Genes encoding insect odorant receptors and uses thereof

ABSTRACT

This invention provides an isolated nucleic acid molecule encoding an insect odorant receptor. This invention provides a nucleic acid molecule of at least 12 nucleotides capable of specifically hybridizing with the nucleic acid molecule encoding an insect odorant receptor. This invention also provides a purified, insect odorant receptor. This invention provides an antibody capable of specifically binding to an insect odorant receptor. This invention provides a method for identifying cDNA inserts encoding an insect odorant receptors. This invention provides a method of identifying a compound capable of specifically bind to an insect odorant receptor. This invention also provides a method of identifying a compound capable of activating the activity of an insect odorant receptor.

This application is a continuation of U.S. Ser. No. 09/932,227, filedAug. 17, 2001, which is a continuation of PCT International ApplicationNo. PCT/US00/04995, filed Feb. 25, 2000, which was acontinuation-in-part of, and claimed priority of, U.S. Ser. No.09/257,706, filed Feb. 25, 1999, now abandoned, the contents of all ofwhich are hereby incorporated by reference into the subject application.

The invention disclosed herein was made with Government support underNIH:NIMH, 5P50, MH50733-05 and NINDS, NS29832-07 from the Department ofHealth and Human Services. Accordingly, the U.S. Government has certainrights in this invention.

Throughout this application, various publications are referred to byarabic numeral within parentheses. Full citations for these publicationsare presented immediately before the claims. Disclosures of thesepublications in their entireties are hereby incorporated by referenceinto this application in order to more fully describe the state of theart to which this invention pertains.

BACKGROUND OF THE INVENTION

All animals possess a “nose,” an olfactory sense organ that allows forthe recognition and discrimination of chemosensory information in theenvironment. Humans, for example, are thought to recognize over 10,000discrete odors with exquisite discriminatory power such that subtledifferences in chemical structure can often lead to profound differencesin perceived odor quality. What mechanisms have evolved to allow therecognition and discrimination of complex olfactory information and howis olfactory perception ultimately translated into appropriatebehavioral responses? The recognition of odors is accomplished byodorant receptors that reside on olfactory cilia, a specialization ofthe dendrite of the olfactory sensory neuron. The odorant receptor genesencode novel serpentine receptors that traverse the membrane seventimes. In several vertebrate species, and in the invertebrateCaenorhabditis elegans, as many as 1000 genes encode odorant receptors,suggesting that 1-5% of the coding potential of the genome in theseorganisms is devoted to the recognition of olfactory sensory stimuli(Buck and Axel, 1991; Levy et al., 1991; Parmentier et al., 1992;Ben-Arie et al., 1994; Troemel et al., 1995; Sengupta et al., 1996;Robertson, 1998). Thus, unlike color vision in which threephotoreceptors can absorb light across the entire visible spectrum,these data suggest that a small number of odorant receptors areinsufficient to recognize the full spectrum of distinct molecularstructures perceived by the olfactory system. Rather, the olfactorysensory system employs an extremely large number of receptors, eachcapable of recognizing a small number of odorous ligands.

The discrimination of olfactory information requires that the braindiscern which of the numerous receptors have been activated by anodorant. In mammals, individual olfactory sensory neurons express onlyone of a thousand receptor genes such that the neurons are functionallydistinct (Ngai et al., 1993; Ressler et al., 1993; Vassar et al., 1993;Chess et al., 1994). The axons from olfactory neurons expressing aspecific receptor converge upon two spatially invariant glomeruli amongthe 1800 glomeruli within the olfactory bulb (Ressler et al., 1994;Vassar et al., 1994; Mombaerts et al., 1996; Wang et al., 1998). Thebulb therefore provides a spatial map that identifies which of thenumerous receptors has been activated within the sensory epithelium. Thequality of an olfactory stimulus would therefore be encoded by specificcombinations of glomeruli activated by a given odorant.

The logic of olfactory discrimination is quite different in thenematode, C. elegans. Despite the large size of the odorant receptorgene family, volatile odorants are recognized by only three pairs ofchemosensory cells each likely to express a large number of receptorgenes (Bargmann and Horvitz, 1991; Colbert and Bargmann, 1995; Troemelet al., 1995). Activation of any one of the multiple receptors in onecell will lead to chemoattraction, whereas activation of receptors in asecond cell will result in chemorepulsion (Troemel et al., 1997). Thespecific neural circuit activated by a given sensory neuron is thereforethe determinant of the behavioral response. Thus, this invertebrateolfactory sensory system retains the ability to recognize a vast arrayof odorants but has only limited discriminatory power.

Vertebrates create an internal representation of the external olfactoryworld that must translate stimulus features into neural information.Despite the elucidation of a precise spatial map, it has been difficultin vertebrates to discern how this information is decoded to relate therecognition of odors to specific behavioral responses. Genetic analysisof olfactory-driven behavior in invertebrates may ultimately afford asystem to understand the mechanistic link between odor recognition andbehavior. Insects provide an attractive model system for studying theperipheral and central events in olfaction because they exhibitsophisticated olfactory-driven behaviors under control of an olfactorysensory system that is significantly simpler anatomically than that ofvertebrates (Siddiqi, 1987; Carlson, 1996). Olfactory-based associativelearning, for example, is robust in insects and results in discerniblemodifications in the neural representation of odors in the brain (Faberet al., 1998). It may therefore be possible to associate modificationsin defined olfactory connections with in vivo paradigms for learning andmemory.

Olfactory recognition in the fruit fly Drosophila is accomplished bysensory hairs distributed over the surface of the third antennal segmentand the maxillary palp. Olfactory neurons within sensory hairs sendprojections to one of 43 glomeruli within the antennal lobe of the brain(Stocker, 1994; Laissue et al., 1999). The glomeruli are innervated bydendrites of the projection neurons, the insect equivalent of the mitralcells in the vertebrate olfactory bulb, whose cell bodies surround theglomeruli. These antennal lobe neurons in turn project to the mushroombody and lateral horn of the protocerebrum (reviewed in Stocker, 1994).2-deoxyglucose mapping in the fruit fly (Rodrigues, 1988) and calciumimaging in the honeybee (Joerges et al., 1997; Faber et al., 1998)demonstrate that different odorants elicit defined patterns ofglomerular activity, suggesting that in insects as in vertebrates, atopographic map of odor quality is represented in the antennal lobe.However, in the absence of the genes encoding the receptor molecules, ithas not been possible to define a physical basis for this spatial map.

The present application discloses a large family of genes that arelikely to encode the odorant receptors of Drosophila melanogaster.Difference cloning, along with analysis of Drosophila genomic sequences,has led to the identification of a novel family of putative seventransmembrane domain receptors likely to be encoded by 100 to 200 geneswithin the Drosophila genome. Each receptor is expressed in a smallsubset of sensory cells (0.5-1.5%) that is spatially defined within theantenna and maxillary palp. Moreover, different neurons express distinctcomplements of receptor genes such that individual neurons arefunctionally distinct. Identification of a large family of putativeodorant receptors in insects indicates that, as in other species, thediversity and specificity of odor recognition is accommodated by a largefamily of receptor genes. The identification of the family of putativeodorant receptor genes may afford insight into the logic of olfactoryperception in Drosophila.

Insects provide an attractive system for the study of olfactory sensoryperception. The present application identifies a novel family of seventransmembrane domain proteins, encoded by 100 to 200 genes, that islikely to represent the family of Drosophila odorant receptors. Membersof this gene family are expressed in topographically definedsubpopulations of olfactory sensory neurons in either the antenna or themaxillary palp. Sensory neurons express different complements ofreceptor genes, such that individual neurons are functionally distinct.The isolation of candidate odorant receptor genes along with a geneticanalysis of olfactory-driven behavior in insects may ultimately afford asystem to understand the mechanistic link between odor recognition andbehavior.

SUMMARY OF THE INVENTION

This invention provides an isolated nucleic acid encoding an insectodorant receptor.

The invention provides an isolated nucleic acid encoding a polypeptidepresent in an insect odorant receptor which polypeptide comprises seventransmembrane domains and a C-terminal domain, wherein one of the seventransmembrane domains is located within the polypeptide at a positionadjoining the C-terminal domain and wherein this seventh transmembranedomain and the adjoining C-terminal domain together comprise consecutiveamino acids the sequence of which is as follows: (SEQ ID NO: 107) -(F,Y, L, A, T, S or C)-(P, I, M, V, T, L, Q, S or H)-(F, Y, I, S, L, C, Mor V)-(C, Y, T, S, L or A)-(Y, N, F, M, I, L, K, S, H or T)-(X)₂₀-W-;

-   -   wherein each X in (X)₂₀ represents an amino acid and the        identity of each X is independent of the identity of any other        X.

The invention provides an isolated nucleic acid encoding a polypeptidepresent in an insect odorant receptor, wherein the polypeptide isselected from the group consisting of polypeptides comprisingconsecutive amino acids the sequence of which is one of the following:

(a) SEQ ID NO: 2, (b) SEQ ID NO: 4, (c) SEQ ID NO: 6, (d) SEQ ID NO: 8,(e) SEQ ID NO: 10, (f) SEQ ID NO: 12, (g) SEQ ID NO: 14, (h) SEQ ID NO:16, (i) SEQ ID NO: 18, (j) SEQ ID NO: 20, (k) SEQ ID NO: 22, (l) SEQ IDNO: 24, (m) SEQ ID NO: 26, (n) SEQ ID NO: 28, (o) SEQ ID NO: 30, (p) SEQID NO: 32, (q) SEQ ID NO: 34, (r) SEQ ID NO: 36, (s) SEQ ID NO: 38, (t)SEQ ID NO: 40, (u) SEQ ID NO: 42, (v) SEQ ID NO: 44, (w) SEQ ID NO: 46,(x) SEQ ID NO: 48, The invention provides an isolated nucleic acidencoding an odorant receptor protein from an insect, wherein the nucleicacid comprises:

-   -   (a) a nucleic acid sequence given in any one of SEQ ID NOs: 1,        3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35,        37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67,        69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99,        101, 103, or 105; or    -   (b) a nucleic acid sequence degenerate to a sequence of (a) as a        result of the genetic code.

This invention provides a nucleic acid of at least 12 nucleotidescapable of specifically hybridizing with the sequence of any of theherein described nucleic acids. This invention provides a nucleic acidcomprising at least 12 nucleotides which specifically hybridize withnucleic acid having any of the sequences described herein. Thisinvention provides a vector which comprises any of the herein describedisolated nucleic acids. In another embodiment, the vector is a plasmid.

This invention also provides a host vector system for the production ofa polypeptide having the biological activity of an insect odorantreceptor which comprises the above described vector and a suitable host.

This invention provides a method of producing a polypeptide having thebiological activity of an insect odorant receptor which comprisinggrowing the above described host vector system under conditionspermitting production of the polypeptide and recovering the polypeptideso produced.

(y) SEQ ID NO: 50, (z) SEQ ID NO: 52, (aa) SEQ ID NO: 54, (bb) SEQ IDNO: 56, (cc) SEQ ID NO: 58, (dd) SEQ ID NO: 60, (ee) SEQ ID NO: 62, (ff)SEQ ID NO: 64, (gg) SEQ ID NO: 66, (hh) SEQ ID NO: 68, (ii) SEQ ID NO:70, (jj) SEQ ID NO: 72, (kk) SEQ ID NO: 74, (ll) SEQ ID NO: 76, (mm) SEQID NO: 78, (nn) SEQ ID NO: 80, (oo) SEQ ID NO: 82, (pp) SEQ ID NO: 84,(qq) SEQ ID NO: 86, (rr) SEQ ID NO: 88, (ss) SEQ ID NO: 90, (tt) SEQ IDNO: 92, (uu) SEQ ID NO: 94, (vv) SEQ ID NO: 96, (ww) SEQ ID NO: 98, (xx)SEQ ID NO: 100, (yy) SEQ ID NO: 102, (zz) SEQ ID NO: 104, (aaa) SEQ IDNO: 106, or

(bbb) a polypeptide which shares greater than 25% amino acid identitywith any one of the polypeptides of (a)-(aaa), and comprises atransmembrane domain and an adjoining C-terminal domain which togethercomprise consecutive amino acids the sequence of which is as follows:(SEQ ID NO: 107) -(F, Y, L, A, T, S or C)-(P, I, M, V, T, L, Q, S orH)-(F, Y, I, S, L, C, M or V)-(C, Y, T, S, L or A)-(Y, N, F, M, I, L, K,S, H or T)-(X)₂₀-W-;

-   -    wherein each X in (X)₂₀ represents an amino acid and the        identity of each X is independent of the identity of any other        X.

The invention provides an isolated nucleic acid encoding an odorantreceptor protein from an insect, wherein the receptor protein comprisesconsecutive amino acids having a sequence identical to that set forthfor DORA45 in SEQ ID NO: 104.

This invention also provides a purified, insect odorant receptor. Thisinvention further provides a polypeptide encoded by the herein describedisolated nucleic acids.

This invention provides an antibody which specifically binds to aninsect odorant receptor. This invention also provides an antibody whichcompetitively inhibits the binding of the antibody capable ofspecifically binding to an insect odorant receptor.

This invention provides a method for identifying cDNA inserts encodingan insect odorant receptors comprising: (a) generating a cDNA librarywhich contains clones carrying cDNA inserts from antennal or maxillarypalp sensory neurons; (b) hybridizing nucleic acid molecules of theclones from the cDNA libraries generated in step (a) with probesprepared from the antenna or maxillary palp neurons and probes fromheads lacking antenna or maxillary palp neurons or from virgin femalebody tissue; (c) selecting clones which hybridized with probes from theantenna or maxillary palp neurons but not from head lacking antenna ormaxillary palp neurons or virgin female body tissue; and (d) isolatingclones which carry the hybridized inserts, thereby identifying theinserts encoding odorant receptors.

This invention also provides cDNA inserts identified by the abovemethod.

This invention further provides a method for identifying DNA insertsencoding an insect odorant receptors comprising: (a) generating DNAlibraries which contain clones carrying inserts from a sample whichcontains at least one antennal or maxillary palp neuron; (b) contactingclones from the cDNA libraries generated in step (a) with nucleic acidmolecule capable of specifically hybridizing with the sequence whichencodes an insect odorant receptor in appropriate conditions permittingthe hybridization of the nucleic acid molecules of the clones and thenucleic acid molecule; (c) selecting clones which hybridized with thenucleic acid molecule; and (d) isolating the clones which carry thehybridized inserts, thereby identifying the inserts encoding the odorantreceptors.

This invention also provides a method to identify DNA inserts encodingan insect odorant receptors comprising: (a) generating DNA librarieswhich contain clones with inserts from a sample which contains at leastone antenna or maxillary palp sensory neuron; (b) contacting the clonesfrom the DNA libraries generated in step (a) with appropriate polymerasechain reaction primers which specifically bind to nucleic acid moleculesencoding odorant receptors in appropriate conditions permitting theamplification of the hybridized inserts by polymerase chain reaction;(c) selecting the amplified inserts; and (d) isolating the amplifiedinserts, thereby identifying the inserts encoding the odorant receptors.

This invention also provides a method to isolate DNA molecules encodinginsect odorant receptors comprising: (a) contacting a biological sampleknown to contain nucleic acids with appropriate polymerase chainreaction primers which specifically bind to nucleic acid moleculesencoding insect odorant receptors in appropriate conditions permittingthe amplification of the hybridized molecules by polymerase chainreaction; (b) isolating the amplified molecules, thereby identifying theDNA molecules encoding the insect odorant receptors.

This invention also provides a method for obtaining a nucleic acidencoding an insect odorant receptor which comprises:

-   -   (a) contacting a sample containing nucleic acids of insect        origin with primers which comprise a nucleic acid corresponding        to a nucleic acid which encodes consecutive amino acids having        the sequence set forth in SEQ ID NO: 107 and are capable of        specifically binding to a nucleic acid encoding an insect        odorant receptor under appropriate conditions permitting        hybridization of the primers to such nucleic acid to produce a        hybridization product;    -   (b) amplifying the resulting hybridization product using a        polymerase chain reaction; and    -   (c) isolating the amplified molecules, thereby identifying the        DNA molecules encoding the insect odorant receptors.

This invention also provides a method of transforming cells whichcomprises transfecting a host cell with a suitable vector describedabove. This invention also provides transformed cells produced by theabove method.

This invention provides a method of identifying a compound whichspecifically binds to an insect odorant receptor which comprisescontacting a transfected cell or membrane fraction of the abovedescribed transfected cell with an appropriate amount of the compoundunder conditions permitting binding of the compound to such receptor,detecting the presence of any such compound specifically bound to thereceptor, and thereby identifying the compound as a compound whichspecifically binds to the receptor.

This invention provides a method of identifying a compound whichspecifically binds to an insect odorant receptor which comprisescontacting an appropriate amount of the purified insect odorant receptorwith an appropriate amount of the compound under conditions permittingbinding of the compound to such purified receptor, detecting thepresence of any such compound specifically bound to the receptor, andthereby determining identifying the compound as a compound whichspecifically binds to the receptor.

This invention also provides a method of identifying a compound whichactivates an insect odorant receptor which comprises contacting thetransfected cells or membrane fractions of the above-describedtransfected cells with the compound under conditions permitting theactivation of a functional odorant receptor response, the activation ofthe receptor indicating that the compound is a compound which activatesan insect odorant receptor.

This invention also provides a method of identifying a compound whichactivates an odorant receptor which comprises contacting a purifiedinsect odorant receptor with the compound under conditions permittingthe activation of a functional odorant receptor response, the activationof the receptor indicating that the compound is a compound whichactivates an insect odorant receptor. In an embodiment, the purifiedreceptor is embedded in a lipid bilayer.

This invention also provides a method of identifying a compound whichinhibits the activity of an insect odorant receptor which comprisescontacting the transfected cells or membrane fractions of theabove-described transfected cells with an appropriate amount of thecompound under conditions permitting the inhibition of a functionalodorant receptor response, the inhibition of the receptor responseindicating that the compound is a compound which inhibits the activityof an insect odorant receptor.

This invention provides a method of identifying a compound whichinhibits the activity of an insect odorant receptor which comprisescontacting an appropriate amount of the purified insect odorant receptorwith an appropriate amount of the compound under conditions permittingthe inhibition of a functional odorant receptor response, the inhibitionof the receptor response indicating that the compound is a compoundwhich inhibits the activity of a odorant receptor. In an embodiment, thepurified receptor is embedded in a lipid bilayer.

This invention also provides the compound identified by any of theabove-described methods.

This invention provides a method of controlling pest populations whichcomprises identifying odorant ligands by the above-described methodwhich are alarm odorant ligands and spraying the desired area with theidentified odorant ligands.

This invention provides a method of controlling a pest population whichcomprises identifying odorant ligands by the above-described methodwhich interfere with the interaction between the odorant ligands and theodorant receptors which are associated with fertility.

BRIEF DESCRIPTION OF FIGURES

FIG. 1A-1D Identification of Rare Antennal- and Maxillary Palp-SpecificGenes

Candidate antennal/maxillary palp-specific phage were subjected to invivo excision, digestion of resulting pBLUESCRIPT plasmid DNAs withBamHI/Asp718, and electrophoresis on 1.5% agarose gels. Southern blotswere hybridized with ³²P-labeled cDNA probes generated fromantennal/maxillary palp mRNA (Panel A), head minus antennal/maxillarypalp mRNA (Panel B), or virgin female body mRNA (Panel C). The ethidiumbromide stained gel is shown in Panel D. Of the thirteen clonesdisplayed in this figure, four appear to be antennal/maxillary palpspecific (lanes 5, 7, 9, and 11). However, only two are selectivelyexpressed in subsets of cells in chemosensory organs of the adult fly.DOR104, a putative maxillary palp odorant receptor, is in Lane 9. Theclone in Lane 11 (RN106) is homologous to lipoprotein and triglyceridelipases and is expressed in a restricted domain in the antenna (data notshown).

FIG. 2A-2C Expression of DOR104 in a Subset of Maxillary Palp Neurons

(A) A frontal section of an adult maxillary palp was hybridized with adigoxigenin-labeled antisense RNA probe and visualized withanti-digoxigenin conjugated to alkaline phosphatase. Seven cellsexpressing DOR104 are visible in this 15 μm section, which representsabout one third of the diameter of the maxillary palp. Serial sectionsof multiple maxillary palps were scored for DOR104 expression and onaverage 20 cells per maxillary palp are positive for this receptor.

(B) Transgenic flies carrying a DOR104-lacZ reporter transgene werestained with X-GAL in a whole mount preparation. Maxillary palps weredissected from the head and viewed in a flattened cover slippedpreparation under Nomarski optics, which allows the visualization of all20 cells expressing DOR104-lacZ.

(C) Dendrites and axons of neurons expressing DOR104-lacZ are visible inthis horizontal section of a maxillary palp. LacZ expression wasvisualized with a polyclonal anti-β-galactosidase primary antibody and aCY3-conjugated secondary antibody. Sections were viewed underepifluorescence and photographed on black and white film.

FIG. 3A-3B Predicted Amino Acid Sequences of Drosophila Odorant ReceptorGenes

Deduced amino acid sequences of 12 DOR genes are aligned using ClustalW(MacVector, Oxford Molecular). Predicted positions of transmembraneregions (I-VII) are indicated by rectangular boxes above the alignment.Amino acids identities are marked with black shading and similaritiesare indicated with light shading. Protein sequences of DOR87 (SEQ ID NO:6), DOR53 (SEQ ID NO: 8), DOR67 (SEQ ID NO: 10), DOR104 (SEQ ID NO: 4),and DOR64 (SEQ ID NO: 12) were derived from cDNA clones. All others werederived from GENSCAN predictions of intron-exon arrangements in genomicDNA, as indicated by the letter “g” after the gene name.

FIG. 4A-4I Receptor Gene Expression in Spatially Restricted Regions ofthe Antenna

Digoxigenin-labeled antisense RNA probes against 8 DOR genes eachhybridize to a small number of cells distributed in distinct regions inthe antenna. The total number of cells per antenna expressing a givenreceptor was obtained by counting positive cells in serial sections ofmultiple antennae. There are approximately 20 positive cells per antennafor DOR67 (A), DOR53 (B), and DOR24 (data not shown); 15 positive cellsfor DOR62 (C) and DOR87 (D); and 10 positive cells for DOR64 (E). Theactual number of cells staining in these sections is a subset of thistotal number. With the exception of DOR53 and DOR67, which stronglycross-hybridize, the receptor genes likely identify different olfactoryneurons, such that the number of cells staining with a mixed probe (F)is equal to the sum of those staining with the individual probes (A-E).The mixture of DOR53, 67, 62, 87 and 64 labels a total of about 60 cellsper antenna. A total of 34 cells stain with the mixed probe in this 15μm section. Expression of the linked genes DOR71g, DOR72g, and DOR73g isshown in panels (G), (H), and (I), respectively. DOR71g is expressed inapproximately 10 cells in the maxillary palp. Five positive cells areseen in the horizontal section in panel (G). The expression of the othermembers of this linkage group was also examined. DOR72g was found inapproximately 15 cells (of which 3 label in this section) (H) and DOR73gin 1 to 2 cells per antenna (I).

FIG. 5A-5G Odorant Receptors are Restricted to Distinct Populations ofOlfactory Neurons

(A-C) Flies of the C155 elav-GAL4; UAS-lacZ genotype express cytoplasmiclacZ in all neuronal cells. Panels (A-C) show confocal images of ahorizontal maxillary palp section from such a fly incubated with anantisense RNA probe against DOR104 (red) and anti-β-galactosidaseantibody (green). DOR104 recognizes five cells in this maxillary palpsection (A), all of which also express elav-lacZ (B), as demonstrated bythe yellow cells in the merged image in panel (C).

(D, E) DOR64 and DOR87 are expressed in non-overlapping neurons at thetip of the antenna. Antisense RNA probes for DOR64 (digoxigenin-RNA;red) and DOR87 (FITC-RNA; green) were annealed to the same antennalsections and viewed by confocal microscopy. Panel (D) is a digitalsuperimposition of confocal images taken at 0.5 μm intervals through a10 μm section of the antenna. Cells at different focal planes expressboth receptors, but no double labeled cells are found.

(F, G) Two color RNA in situ hybridization with odorant receptors andodorant binding proteins demonstrates that these proteins are expressedin different populations of cells. DOR53 (FITC-RNA; green) labels a fewcells internal to the cuticle at the proximal-medial edge, while PBPRP2(digoxigenin-RNA; red) labels a large number of cells apposed to thecuticle throughout the antenna (F). The more restricted odorant bindingprotein OS-F (digoxigenin-RNA; red) also stains cells distinct fromthose expressing DOR67 (FITC-RNA; green)(G).

FIG. 6A-6F Receptor Expression is Conserved Between Individuals

Frontal sections of antennae from six different individuals werehybridized with digoxigenin-labeled antisense RNA probes against DOR53(A-C) or DOR87 (D-F). DOR53 labels approximately 20 cells on theproximal-medial edge of the antenna, of which approximately 5 are shownlabeling in these sections. DOR87 is expressed in about the same numberof cells at the distal tip. Both the position and number of stainingcells is conserved between different individuals and is not sexuallydimorphic.

FIG. 7A-7E Drosophila Odorant Receptors are Highly Divergent

Oregon R genomic DNA isolated from whole flies was digested with BamHI(B), EcoRI (E), or HindIII (H), electrophoresed on 0.8% agarose gels,and blotted to nitrocellulose membranes. Blots were annealed with³²P-labeled probes derived from DOR53 cDNA (A), DOR67 cDNA (B), or DNAfragments generated by RT-PCR from antennal mRNA for DOR24 (C), DOR62(D), and DOR72g (E). Strong crosshybridization of DOR53 and DOR67 isseen at both high and low stringency (A, B), while DOR24, 62, and 72reveal only a single hybridizing band in each lane at both lowstringency (C-E) and high stringency (data not shown).

FIG. 8 Analysis of axonal projections of olfactory receptor neuronsexpressing a given Drosophila odorant receptor. Result: all neuronsexpressing a given receptor send their axons to a single glomerulus, ordiscrete synaptic structure, in the olfactory processing center of thefly brain. This result is identical to that obtained with mouse odorantreceptors: each glomerulus is dedicated to receiving axonal input fromneurons expressing a given odorant receptor. Therefore, this resultstrengthens the argument that these genes indeed function as odorantreceptors in Drosophila.

FIGS. 9A1-9B ClustalW alignments of two subfamilies of the Drosophilaodorant receptors, the DOR53 (A-1 and A-2) and DOR64 (B) families.

This figure highlights sequence similarities between DOR genes, that arediagnostic hallmarks of the proteins. Residues that are identical indifferent DOR genes are highlighted in black shading, while residuesthat are similar are highlighted in light shading.

DETAILED DESCRIPTION OF THE INVENTION

In order to facilitate an understanding of the Experimental Proceduressection which follow, certain frequently occurring methods and/or termsare described in Sambrook, et al. (1989).

Throughout this application, the following standard abbreviations areused throughout the specification to indicate specific nucleotides:

-   -   C=cytosine A=adenosine    -   T=thymidine G=guanosine.

This invention provides an isolated nucleic acid molecule encoding aninsect odorant receptor. The nucleic acid includes but is not limited toDNA, cDNA, genomic DNA, synthetic DNA or RNA. In an embodiment, thenucleic acid molecule encodes a Drosophila odorant receptor.

The invention provides an isolated nucleic acid encoding a polypeptidepresent in an insect odorant receptor which polypeptide comprises seventransmembrane domains and a C-terminal domain, wherein one of the seventransmembrane domains is located within the polypeptide at a positionadjoining the C-terminal domain and wherein this seventh transmembranedomain and the adjoining C-terminal domain together comprise consecutiveamino acids the sequence of which is as follows: (SEQ ID NO: 107) -(F,Y, L, A, T, S or C)-(P, I, M, V, T, L, Q, S or H)-(F, Y, I, S, L, C, Mor V)-(C, Y, T, S, L or A)-(Y, N, F, M, I, L, K, S, H or T)-(X)₂₀-W-;

-   -   wherein each X in (X)₂₀ represents an amino acid and the        identity of each X is independent of the identity of any other        X.

In one embodiment, the seventh transmembrane domain and the adjoiningC-terminal domain together comprise consecutive amino acids the sequenceof which is as follows: (SEQ ID NO: 111) -(F, Y, L, A or T)-(P, I, M, Vor T)-(F, Y, I, S, L or C)-(C, Y or T)-(Y, N, F, M or I)-(X)₂₀-W-.

In one embodiment, the seventh transmembrane domain and the adjoiningC-terminal domain together comprise consecutive amino acids the sequenceof which is as follows: (SEQ ID NO: 109) -(F, Y or L)-(P, I, M, V orT)-(F, Y, I, S, L or C)-(C, Y or T)-(Y, N or F)-(X)₂₀-W-.

In one embodiment, the seventh transmembrane domain and the adjoiningC-terminal domain together comprise consecutive amino acids the sequenceof which is as follows: (SEQ ID NO: 112) -F-P-X-C-Y-(X)₂₀-W-.

The invention provides an isolated nucleic acid encoding a polypeptidepresent in an insect odorant receptor, wherein the polypeptide isselected from the group consisting of polypeptides comprisingconsecutive amino acids the sequence of which is one of the following:

(a) SEQ ID NO: 2, (b) SEQ ID NO: 4, (c) SEQ ID NO: 6, (d) SEQ ID NO: 8,(e) SEQ ID NO: 10, (f) SEQ ID NO: 12, (g) SEQ ID NO: 14, (h) SEQ ID NO:16, (i) SEQ ID NO: 18, (j) SEQ ID NO: 20, (k) SEQ ID NO: 22, (l) SEQ IDNO: 24, (m) SEQ ID NO: 26, (n) SEQ ID NO: 28, (o) SEQ ID NO: 30, (p) SEQID NO: 32, (q) SEQ ID NO: 34, (r) SEQ ID NO: 36, (s) SEQ ID NO: 38, (t)SEQ ID NO: 40, (u) SEQ ID NO: 42, (v) SEQ ID NO: 44, (w) SEQ ID NO: 46,(x) SEQ ID NO: 48, (y) SEQ ID NO: 50, (z) SEQ ID NO: 52, (aa) SEQ ID NO:54, (bb) SEQ ID NO: 56, (cc) SEQ ID NO: 58, (dd) SEQ ID NO: 60, (ee) SEQID NO: 62, (ff) SEQ ID NO: 64, (gg) SEQ ID NO: 66, (hh) SEQ ID NO: 68,(ii) SEQ ID NO: 70, (jj) SEQ ID NO: 72, (kk) SEQ ID NO: 74, (ll) SEQ IDNO: 76, (mm) SEQ ID NO: 78, (nn) SEQ ID NO: 80, (oo) SEQ ID NO: 82, (pp)SEQ ID NO: 84, (qq) SEQ ID NO: 86, (rr) SEQ ID NO: 88, (ss) SEQ ID NO:90, (tt) SEQ ID NO: 92, (uu) SEQ ID NO: 94, (vv) SEQ ID NO: 96, (ww) SEQID NO: 98, (xx) SEQ ID NO: 100, (yy) SEQ ID NO: 102, (zz) SEQ ID NO:104, (aaa) SEQ ID NO: 106, or

(bbb) a polypeptide which shares greater than 25% amino acid identitywith any one of the polypeptides of (a)-(aaa), and comprises atransmembrane domain and an adjoining C-terminal domain which togethercomprise consecutive amino acids the sequence of which is as follows:(SEQ ID NO: 107) -(F, Y, L, A, T, S or C)-(P, I, M, V, T, L, Q, S orH)-(F, Y, I, S, L, C, M or V)-(C, Y, T, S, L or A)-(Y, N, F, M, I, L, K,S, H or T)-(X)₂₀-W-;

-   -    wherein each X in (X)₂₀ represents an amino acid and the        identity of each X is independent of the identity of any other        X.

In one embodiment, the nucleic acid encodes a polypeptide which sharesgreater than 35% amino acid identity with any one of the polypeptides of(a)-(aaa). In one embodiment, the nucleic acid encodes a polypeptidewhich shares greater than 45% amino acid identity with any one of thepolypeptides of (a)-(aaa). In one embodiment, the nucleic acid encodes apolypeptide which shares greater than 55% amino acid identity with anyone of the polypeptides of (a)-(aaa). In one embodiment, the nucleicacid encodes a polypeptide which shares greater than 65% amino acididentity with any one of the polypeptides of (a)-(aaa). In oneembodiment, the nucleic acid encodes a polypeptide which shares greaterthan 75% amino acid identity with any one of the polypeptides of(a)-(aaa).

The invention provides an isolated nucleic acid encoding a polypeptidepresent in an insect odorant receptor, wherein the nucleic acidhybridizes under high stringency to a complement of any of the nucleicacids disclosed herein. The invention also provides an isolated nucleicacid encoding a polypeptide present in an insect odorant receptor,wherein the nucleic acid hybridizes under high stringency to any of thenucleic acids disclosed herein.

The invention provides an isolated nucleic acid encoding a polypeptidepresent in an insect odorant receptor, wherein the polypeptide comprisesconsecutive amino acids having a sequence identical to that set forthfor DORA45 in SEQ ID NO: 104.

The invention provides an isolated nucleic acid encoding a polypeptidepresent in an insect odorant receptor, wherein the nucleic acidcomprises:

-   -   (a) a nucleic acid sequence given in any one of SEQ ID NOs: 1,        3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35,        37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67,        69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99,        101, 103, or 105; or    -   (b) a nucleic acid sequence degenerate to a sequence of (a) as a        result of the genetic code.

In one embodiment, the insect odorant receptor comprises seventransmembrane domains.

In different embodiments of any of the isolated nucleic acids describedherein, the nucleic acid is DNA or RNA. In different embodiments, theDNA is cDNA, genomic DNA, or synthetic DNA. In different embodiments,the RNA is synthetic RNA.

In one embodiment of any of the isolated nucleic acids described herein,the nucleic acid molecule encodes a Drosophila odorant receptor.

The nucleic acids encoding an insect odorant receptor includes moleculescoding for polypeptide analogs, fragments or derivatives of antigenicpolypeptides which differ from naturally-occurring forms in terms of theidentity or location of one or more amino acid residues (deletionanalogs containing less than all of the residues specified for theprotein, substitution analogs wherein one or more residues specified arereplaced by other residues and addition analogs where in one or moreamino acid residues is added to a terminal or medial portion of thepolypeptides) and which share some or all properties ofnaturally-occurring forms.

These molecules include but not limited to: the incorporation of codons“preferred” for expression by selected non-mammalian hosts; theprovision of sites for cleavage by restriction endonuclease enzymes; andthe provision of additional initial, terminal or intermediate sequencesthat facilitate construction of readily expressed vectors. Accordingly,these changes may result in a modified insect odorant receptor. It isthe intent of this invention to include nucleic acid molecules whichencode modified insect odorant receptors. Also, to facilitate theexpression of receptors in different host cells, it may be necessary tomodify the molecule such that the expressed receptors may reach thesurface of the host cells. The modified insect odorant receptor shouldhave biological activities similar to the unmodified insect odorantreceptor. The molecules may also be modified to increase the biologicalactivity of the expressed receptor.

The invention provides a nucleic acid comprising at least 12 nucleotideswhich specifically hybridizes with any of the isolated nucleic acidsdescribed herein. In one embodiment, the nucleic acid hybridizes with aunique sequence within the sequence of any of the nucleic acid moleculesdescribed herein. In different embodiments, the nucleic acid is DNA,cDNA, genomic DNA, synthetic DNA or RNA.

This invention provides a nucleic acid probe which comprises:

-   -   (a) a nucleic acid sequence given in any one of SEQ ID NOs: 1,        3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35,        37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67,        69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99,        101, 103, or 105; or    -   (b) a nucleic acid sequence degenerate to a sequence of (a) as a        result of the genetic code; or    -   (c) a portion of a nucleic acid sequence of (a) or (b) which        encodes consecutive amino acids having the sequence set forth in        SEQ ID NO: 107.

In an embodiment, the probes are cDNA probes.

This invention provides a vector which comprises any of the isolatednucleic acids described herein. In one embodiment, the vector is aplasmid.

In one embodiment of the vector, the isolated nucleic acids describedherein is operatively linked to a regulatory element. Regulatoryelements required for expression include promoter sequences to bind RNApolymerase and transcription initiation sequences for ribosome binding.For example, a bacterial expression vector includes a promoter such asthe lac promoter and for transcription initiation the Shine-Dalgarnosequence and the start codon AUG. Similarly, a eukaryotic expressionvector includes a heterologous or homologous promoter for RNA polymeraseII, a downstream polyadenylation signal, the start codon AUG, and atermination codon for detachment of the ribosome. Such vectors may beobtained commercially or assembled from the sequences described bymethods well-known in the art, for example the methods described hereinfor constructing vectors in general.

The invention provides a host vector system for production of apolypeptide having the biological activity of an insect odorantreceptor, which comprises any of the vectors described herein and asuitable host. In different embodiments, the suitable host is abacterial cell, a yeast cell, an insect cell, or an animal cell.

The host cell of the expression system described herein may be selectedfrom the group consisting of the cells where the protein of interest isnormally expressed, or foreign cells such as bacterial cells (such as E.coli), yeast cells, fungal cells, insect cells, nematode cells, plant oranimal cells, where the protein of interest is not normally expressed.Suitable animal cells include, but are not limited to Vero cells, HeLacells, Cos cells, CV1 cells and various primary mammalian cells.

The invention provides a method of producing a polypeptide having thebiological activity of an insect odorant receptor which comprisinggrowing any of the host vector systems described herein under conditionspermitting production of the polypeptide and recovering the polypeptideso produced.

The invention provides a purified insect odorant receptor proteinencoded by any of the isolated nucleic acids described herein. Thisinvention further provides a polypeptide encoded by any of the isolatednucleic acids described herein.

The invention provides an antibody which specifically binds to an insectodorant receptor protein encoded by any of the isolated nucleic acidsdescribed herein. In one embodiment, the antibody is a monoclonalantibody. In another embodiment, the antibody is polyclonal. Theinvention provides an antibody which competitively inhibits the bindingof any of the antibodies described herein capable of specificallybinding to an insect odorant receptor. In one embodiment, the antibodyis a monoclonal antibody. In another embodiment, the antibody ispolyclonal.

Monoclonal antibody directed to an insect odorant receptor may comprise,for example, a monoclonal antibody directed to an epitope of an insectodorant receptor present on the surface of a cell. Amino acid sequencesmay be analyzed by methods well known to those skilled in the art todetermine whether they produce hydrophobic or hydrophilic regions in theproteins which they build. In the case of cell membrane proteins,hydrophobic regions are well known to form the part of the protein thatis inserted into the lipid bilayer which forms the cell membrane, whilehydrophilic regions are located on the cell surface, in an aqueousenvironment.

Antibodies directed to an insect odorant receptor may be serum-derivedor monoclonal and are prepared using methods well known in the art. Forexample, monoclonal antibodies are prepared using hybridoma technologyby fusing antibody producing B cells from immunized animals with myelomacells and selecting the resulting hybridoma cell line producing thedesired antibody. Cells such as NIH3T3 cells or 293 cells which expressthe receptor may be used as immunogens to raise such an antibody.Alternatively, synthetic peptides may be prepared using commerciallyavailable machines.

As a still further alternative, DNA, such as a cDNA or a fragmentthereof, encoding the receptor or a portion of the receptor may becloned and expressed. The expressed polypeptide may be recovered andused as an immunogen.

The resulting antibodies are useful to detect the presence of insectodorant receptors or to inhibit the function of the receptor in livinganimals, in humans, or in biological tissues or fluids isolated fromanimals or humans.

This antibodies may also be useful for identifying or isolating otherinsect odorant receptors. For example, antibodies against the Drosophilaodorant receptor may be used to screen an cockroach expression libraryfor a cockroach odorant receptor. Such antibodies may be monoclonal ormonospecific polyclonal antibody against a selected insect odorantreceptor. Different insect expression libraries are readily availableand may be made using technologies well-known in the art.

One means of isolating a nucleic acid molecule which encodes an insectodorant receptor is to probe a libraries with a natural or artificiallydesigned probes, using methods well known in the art. The probes may beDNA or RNA. The library may be cDNA or genomic DNA.

The invention provides a method for identifying cDNA inserts encodinginsect an odorant receptor which comprises:

-   -   (a) generating a cDNA library which contains clones carrying        cDNA inserts from antennal or maxillary palp sensory neurons;    -   (b) hybridizing nucleic acid molecules of the clones from the        cDNA libraries generated in step (a) with probes prepared from        the antenna or maxillary palp neurons and probes from heads        lacking antenna or maxillary palp neurons or from virgin female        body tissue;    -   (c) selecting clones which hybridized with probes from the        antenna or maxillary palp neurons but not from head lacking        antenna or maxillary palp neurons or virgin female body tissue;        and    -   (d) isolating clones which carry the hybridized inserts, thereby        identifying inserts encoding an odorant receptor.

In one embodiment, the method described herein, after step (c), furthercomprises:

-   -   (a) amplifying the inserts from the selected clones by        polymerase chain reaction;    -   (b) hybridizing the amplified inserts with probes from the        antennal or maxillary palp neurons; and    -   (c) isolating the clones which carry the hybridized inserts,        thereby identifying inserts encoding the odorant receptor.

The invention provides a method for identifying a cDNA insert encodingan insect odorant receptor which comprises:

-   -   (a) generating a cDNA library comprising clones carrying cDNA        inserts from antennal or maxillary palp sensory neurons from an        insect;    -   (b) hybridizing nucleic acids of the clones from the cDNA        libraries generated in step (a) with a probe which comprises (i)        a nucleic acid sequence given in any one of SEQ ID NOs: 1, 3, 5,        7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37,        39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69,        71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101,        103, or 105; or (ii) a nucleic acid sequence degenerate to a        sequence of (i) as a result of the genetic code; or (iii) a        portion of a nucleic acid sequence of (i) or (ii) which encodes        consecutive amino acids having the sequence set forth in SEQ ID        NO: 107; and    -   (c) isolating the resulting hybridized nucleic acids so as to        thereby identify the cDNA insert encoding the insect odorant        receptor.

This invention provides a method for identifying a cDNA insert encodingan insect odorant receptor which comprises:

-   -   (a) generating a cDNA library comprising clones carrying cDNA        inserts from antennal or maxillary palp sensory neurons from an        insect;    -   (b) hybridizing nucleic acids of the clones from the cDNA        libraries generated in step (a) with a probe which comprises (i)        a nucleic acid sequence given in any one of SEQ ID NOs: 1, 3, 5,        7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37,        39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69,        71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101,        103, or 105; or (ii) a nucleic acid sequence degenerate to a        sequence of (i) as a result of the genetic code; or (iii) a        portion of a nucleic acid sequence of (i) or (ii) which encodes        consecutive amino acids having the sequence set forth in SEQ ID        NO: 107; and    -   (c) isolating the hybridized inserts, thereby identifying a cDNA        insert encoding an insect odorant receptor.

The appropriate polymerase chain reaction primers may be chosen from theconserved regions of the known insect odorant receptor sequences.Alternatively, the primers may be chosen from the regions which are theactive sites for the binding of ligands.

In one embodiment of any of the methods described herein, the insectodorant receptor is encoded by any of the isolated nucleic acidmolecules described herein.

The invention provides the cDNA inserts identified by any of the methodsdescribed herein.

The invention provides a method for identifying a cDNA insert encodingan insect odorant receptor which comprises:

-   -   (a) generating cDNA libraries which contain clones carrying        inserts from a sample which contains at least one antennal or        maxillary palp neuron;    -   (b) contacting clones from the cDNA libraries generated in        step (a) with any of the nucleic acid molecules described herein        which specifically hybridize with any of the isolated nucleic        acid molecules described herein which encode an insect odorant        receptor protein, in conditions permitting hybridization of the        nucleic acid molecules of the clones and the nucleic acid        molecule;    -   (c) selecting clones which hybridized with the nucleic acid        molecule; and    -   (d) isolating the clones which carry the hybridized inserts,        thereby identifying inserts encoding the odorant receptor.

The invention provides a method for identifying cDNA inserts encoding aninsect odorant receptor which comprises:

-   -   (a) generating cDNA libraries which contain clones with inserts        from a sample which contains at least one antenna or maxillary        palp sensory neuron;    -   (b) contacting the clones from the cDNA libraries generated in        step (a) with appropriate polymerase chain reaction primers        capable of specifically binding to nucleic acid molecules        encoding odorant receptors in appropriate conditions permitting        the amplification of the hybridized inserts by polymerase chain        reaction;    -   (c) selecting the amplified inserts; and    -   (d) isolating the amplified inserts, thereby identifying the        inserts encoding the odorant receptor.

In one embodiment, the insect odorant receptor is encoded by any of theisolated nucleic acids described herein.

The invention provides the cDNA inserts identified by any of the methodsdescribed herein.

This invention provides a method for identifying a cDNA insert encodingan odorant receptor from an insect which comprises:

-   -   (a) generating cDNA libraries which contain clones carrying cDNA        inserts from the insect;    -   (b) contacting the cDNA libraries containing the clones        generated in step (a) with any of the nucleic acid molecules        described herein which specifically hybridize with any of the        isolated nucleic acid molecules described herein which encode an        insect odorant receptor protein under conditions permitting        hybridization of the clones and the nucleic acid;    -   (c) selecting clones which hybridized with the nucleic acid; and    -   (d) isolating the hybridized clones which contain the cDNA        inserts so as to thereby identify inserts encoding the odorant        receptor from the insect.

The invention provides a method for obtaining a nucleic acid encoding anodorant receptor from an insect which comprises:

-   -   (a) contacting a sample containing nucleic acid of insect origin        with primers which comprise nucleic acid corresponding to a        nucleic acid which encodes an amino acid sequence set forth in        SEQ ID NO: 107 under appropriate conditions permitting        hybridization of the primers to the nucleic acid of insect        origin to produce a hybridization product;    -   (b) amplifying the resulting hybridization product using a        polymerase chain reaction; and    -   (c) isolating the amplified molecules, thereby obtaining a        nucleic acid encoding an odorant receptors from an insect.

This invention provides a method for obtaining a nucleic acid encodingan odorant receptor from an insect which comprises:

-   -   (a) contacting a sample containing nucleic acid of insect origin        with polymerase chain reaction primers which specifically        hybridize with nucleic acid which encodes an amino acid sequence        set forth in SEQ ID NO: 107 under appropriate conditions        permitting hybridization of the primers to the nucleic acid to        produce a hybridization product;    -   (b) amplifying the resulting hybridization product using a        polymerase chain reaction; and    -   (c) isolating the amplified molecules, thereby obtaining a        nucleic acid encoding an odorant receptor from an insect.

In one embodiment, the insect odorant receptor is encoded by any of theisolated nucleic acids described herein.

This invention also provides a method to isolate DNA molecules encodinginsect odorant receptors comprising: (a) contacting a biological sampleknown to contain nucleic acids with appropriate polymerase chainreaction primers capable of specifically binding to nucleic acidmolecules encoding insect odorant receptors in appropriate conditionspermitting the amplification of the hybridized molecules by polymerasechain reaction; (b) isolating the amplified molecules, therebyidentifying the DNA molecules encoding the insect odorant receptors.

This invention provides a cDNA insert encoding an insect odorantreceptor obtainable by the following method:

-   -   (a) generating cDNA libraries which contain clones carrying cDNA        inserts from the insect;    -   (b) contacting the cDNA libraries containing the clones        generated in step (a) with any of the nucleic acid molecules        described herein which specifically hybridize with any of the        isolated nucleic acid molecules described herein which encode an        insect odorant receptor protein under conditions permitting        hybridization of the clones and the nucleic acid;    -   (c) selecting clones which hybridized with the nucleic acid; and    -   (d) isolating the hybridized clones which contain the cDNA        inserts so as to thereby identify inserts encoding the odorant        receptor from the insect.

The invention provides a method of transforming a cell which comprisestransfecting a host cell with any of the vectors described herein.

The invention provides a transformed cell produced by any of the methodsdescribed herein. In one embodiment, prior to being transfected with thevector the host cell does not express an insect odorant receptor. In oneembodiment, prior to being transfected with the vector the host celldoes express an insect odorant receptor.

The invention provides a method of identifying a compound whichspecifically binds to an insect odorant receptor which comprisescontacting any of the transformed cells described herein, or a membranefraction from said cells, with the compound under conditions permittingbinding of the compound to the odorant receptor, detecting the presenceof any such compound specifically bound to the receptor, and therebyidentifying the compound as a compound which specifically binds to aninsect odorant receptor.

The invention provides a method of identifying a compound whichspecifically binds to an insect odorant receptor which comprisescontacting any of the purified insect odorant receptor proteinsdescribed herein with the compound under conditions permitting bindingof the compound to the purified odorant receptor protein, detecting thepresence of any such compound specifically bound to the receptor, andthereby identifying the compound as a compound which specifically bindsto an insect odorant receptor. In one embodiment, the purified insectodorant receptor protein is embedded in a lipid bilayer. The purifiedreceptor may be embedded in the liposomes with proper orientation tocarry out normal functions. Liposome technology is well-known in theart.

The invention provides a method of identifying a compound whichactivates an insect odorant receptor which comprises contacting any ofthe transformed cells described herein, or a membrane fraction from saidcells, with the compound under conditions permitting activation of theodorant receptor, detecting activation of the receptor, and therebyidentifying the compound as a compound which activates an insect odorantreceptor.

The invention provides a method of identifying a compound whichactivates an insect odorant receptor which comprises contacting any ofthe purified insect odorant receptor proteins described herein with thecompound under conditions permitting activation of the odorant receptor,detecting activation of the receptor, and thereby identify the compoundas a compound which activates an insect odorant receptor. In oneembodiment, the purified insect odorant receptor protein is embedded ina lipid bilayer. The purified receptor may be embedded in the liposomeswith proper orientation to carry out normal functions. Liposometechnology is well-known in the art.

The invention provides a method of identifying a compound which inhibitsthe activity of an insect odorant receptor which comprises contactingany of the transformed cells described herein, or a membrane fractionfrom said cells, with the compound under conditions permittinginhibition of the activity of the odorant receptor, detecting inhibitionof the activity of the receptor, and thereby identifying the compound asa compound which inhibits the activity of an insect odorant receptor.

The invention provides a method of identifying a compound which inhibitsthe activity of an insect odorant receptor which comprises contactingany of the purified insect odorant receptor proteins described hereinwith the compound under conditions permitting inhibition of the activityof the odorant receptor, detecting inhibition of the activity of thereceptor, and thereby identifying the compound as a compound whichinhibits the activity of an insect odorant receptor. In one embodiment,the purified insect odorant receptor protein is embedded in a lipidbilayer. The purified receptor may be embedded in the liposomes withproper orientation to carry out normal functions. Liposome technology iswell-known in the art.

In one embodiment of any of the methods described herein, the compoundis not previously known to specifically bind to an insect odorantreceptor. In one embodiment, the compound is not previously known toactivate an insect odorant receptor. In one embodiment, the compound isnot previously known to inhibit the activity of an insect odorantreceptor.

The invention provides a compound identified by any of the methodsdescribed herein.

In one embodiment, the compound is an alarm odorant ligand. In oneembodiment, the compound is an odorant ligand associated with fertilityof the insect.

The invention provides a method of controlling a population of an insectin an area which comprises identifying a compound using any of themethods described herein and spraying the area with the compound. In oneembodiment, the compound is an alarm odorant ligand or a ligandassociated with fertility of the insect.

The invention provides a method of controlling a population of an insectwhich comprises using a compound identified by any of the methodsdescribed herein, wherein the compound interferes with an interactionbetween an odorant ligand and an odorant receptor, which interaction isassociated with fertility of the insect.

This invention provides a method of preparing a composition whichcomprises identifying a compound using any of the methods describedherein, recovering the compound free of any insect odorant receptor, andadmixing a carrier.

This invention will be better understood from the ExperimentalProcedures which follow. However, one skilled in the art will readilyappreciate that the specific methods and results discussed are merelyillustrative of the invention as described more fully in the claimswhich follow thereafter.

Experimental Procedures

Experimental Animals

Oregon R flies (Drosophila melanogaster) were raised on standardcornmeal-agar-molasses medium at 25° C. Transgenic constructs wereinjected into yw embryos. C155 elav-GAL4 flies were obtained from CoreyGoodman (Lin and Goodman, 1994) and Gary Struhl provided theUAS-(cytoplasmic) lacZ stock.

Preparation and Differential Screening of a DrosophilaAntennal/Maxillary Pale cDNA Library

Drosophila antennae and maxillary palps were obtained by manuallydecapitating and freezing 5000 adult flies and shaking antennae andmaxillary palps through a fine metal sieve. mRNA was prepared using apolyA+ RNA Purification Kit (Stratagene). An antennal/maxillary palpcDNA library was made from 0.5 μg mRNA using the LambdaZAPIIXR kit fromStratagene.

Briefly, phage were plated at low density (500-1000 pfu/150 mm plate)and UV-crosslinked after lifting in triplicate to Hybond-N+ (Amersham).Complex probes were generated by random primed labeling (PrimeItII,Stratagene) of reverse transcribed mRNA (RT-PCR kit, Stratagene) fromvirgin adult female body mRNA and duplicate lifts hybridized at highstringency for 36 hours (65° C. in 0.5M Sodium Phosphate buffer (pH7.3)containing 1% bovine serum albumin, 4% SDS, and 0.5 mg/ml herring spermDNA). The third lift was prescreened with a mix of all previously clonedOBPs/PBPs (McKenna et al., 1994; Pikielny et al., 1994; Kim et al.,1998) remove a source of abundant but undesired olfactory-specificclones. Approximately 5000 individual OBP/PBP and virgin female bodynegative phage clones were isolated, their inserts amplified by PCR withT3 and T7 primers, and approximately 3 μg of DNA were electrophoresed on1.5% agarose gels. Gels were blotted in duplicate to Hybond-N+(Amersham), filters were UV-crosslinked, and the resulting Southernblots were subjected to reverse Northern analysis using complex probesgenerated from virgin female body mRNA. Approximately 500 clones nothybridizing with virgin female body probes were identified andconsolidated onto secondary Southern blots in triplicate. These blotswere probed with complex probes derived from antennal/maxillary palp,head-minus-antenna/maxillary palp, and virgin female body mRNA. A totalof 210 clones negative with head-minus-antenna/maxillary palp and virginfemale body probes and strongly positive, weakly positive, or negativewith antennal/maxillary palp probes were further analyzed by sequencingand in situ hybridization.

Analysis of Drosophila Genome Project Sequences for TransmembraneProteins

All Drosophila genomic sequences were batch downloaded in April 1998from the Berkeley Drosophila Genome Project (Berkeley Drosophila GenomeProject, unpublished). Genomic P1 sequences were first analyzed with theGENSCAN program (Burge and Karlin, 1997) which predicts intron-exonstructures and generates hypothetical coding sequences (CDS) and openreading frames. GENSCAN predicted proteins shorter than 50 amino acidswere discarded. The remaining open reading frames were used to searchfor putative transmembrane regions greater than 15 amino acids with twoprograms that were obtained from the authors and used in stand-alonemode locally (see Persson and Argos, 1994; Cserzo et al., 1997). TheDense Surface Alignment (DAS) program is available from M. Cserzo(miklos@pugh.bip.bham.ac.uk). TMAP is available by contacting theauthor, Bengt Persson (bpn@mbb.ki.se).

Scripts were written to apply the DAS and TMAP programs repeatedly togenome scale sequence sets. Genes showing significant sequencesimilarity to the NCBI non-redundant protein database using BLASTanalysis (Altschul et al., 1990; Altschul et al., 1997) were eliminated.All scripts required for these computations were written in standardANSI C and run on a SUN Enterprise 3000.

Of 229 novel Drosophila proteins with three or more predictedtransmembrane spanning regions, 35 showed no clear sequence similarityto any known protein and were selected for further analysis by in situhybridization. Probes for in situ hybridization were generated by RT-PCRusing antennal/maxillary palp mRNA as a template.

Map Positions of DOR Genes

The chromosome position of DOR104 was determined by in situhybridization of a biotin-labeled probe to salivary gland polytenechromosome squashes as described (Amrein et al., 1988).

Chromosomal positions of all other DOR genes were based on chromosomeassignments of the P1 clones to which they map, as determined by theBerkeley Drosophila Genome Project (see also Hartl et al., 1994;Kimmerly et al., 1996). DOR62 maps to a cosmid sequenced by the EuropeanDrosophila Genome Project (Siden-Kiamos et al., 1990). RECEPTOR MAPPOSITION P1 CLONE ACCESSION NUMBER DOR62 (X) 2F 62D9 (EDGP cosmid) DOR67(2L) 22A3 DS00676 DOR53 (2L) 22A2-3 DS05342 DOR64 (2L) 23A1-2 DS06400DOR71g (2L) 33B1-2 DS07071 DOR72g (2L) 33B1-2 DS07071 DOR73g (2L) 33B1-2DS07071 DOR87 (2R) 43B1-2 DS08779 DOR19g (2R) 46F5-6 DS01913 DOR24 (2R)47D6-E2 DS00724 DOR46 (2R) 59D5-7 DS07462 DOR104 (3L) 85B not applicableThe Isolation of DOR cDNA Clones and Southern Blotting

3×10⁶ clones of the antennal/maxillary palp library described above werescreened with PCR probes for the genes DOR87, DOR53, DOR67, DOR64, andDOR62. cDNAs were present at a frequency ranging from 1:200,000 (DOR67)to 1:1,000,000 (DOR62) in the library and their sequences wereremarkably similar to the hypothetical CDS predicted by the GENSCANprogram. The frequency of these genes is similar to that of DOR104,which is present at 1:125,000 in the antennal/maxillary palp library.All sequencing was with ABI cycle sequencing kits and reactions were runon an ABI 310 or 377 sequencing system.

Five μg of Oregon R genomic DNA isolated from whole flies were digestedwith BamHI, EcoRI, or HindIII, electrophoresed on 0.8% agarose gels, andblotted to Nitropure nitrocellulose membranes (Micron Separations Inc.).Blots were baked and annealed with ³²P-labeled probes derived from cDNAprobes of DOR53 and DOR67, or PCR fragments from DOR24, DOR62, andDOR72g. Hybridization was at 42° C. for 36 hours in 5×SSCP,10×Denhardts, 500 μg/ml herring sperm DNA, and either 50% (highstringency) or 25% (low stringency) formamide (Sambrook et al., 1989).Blots were washed for 1 hour in 0.2×SSC, 0.5% SDS at 65° C. (highstringency) or 1×SSC, 0.5% SDS at 42° C. (low stringency).

In Situ Hybridization

RNA in situ hybridization was carried out essentially as described(Schaeren-Wiemers and Gerfin-Moser, 1993). This protocol was modified toinclude detergents in most steps to increase sensitivity and reducebackground. The hybridization buffer contained 50% formamide, 5×SSC,5×Denhardts, 250 μg/ml yeast tRNA, 500 μg/ml herring sperm DNA, 50 μg/mlHeparin, 2.5 mM EDTA, 0.1% Tween-20, 0.25% CHAPS. All antibody stepswere in the presence of 0.1% Triton X-100, and the reaction wasdeveloped in buffer containing 0.1% Tween-20. Slides were mounted inGlycergel (DAKO) and viewed with Nomarski optics.

Fluorescent in situ hybridization was carried out as above with eitherdigoxigenin or FITC labeled RNA probes. The digoxigenin probe wasvisualized with sheep anti-digoxigenin (Boehringer) followed by donkeyanti-sheep CY3 (Jackson). FITC probes were visualized with mouseanti-FITC (Boehringer) and goat anti-mouse Alexa 488 (Molecular Probes)following preincubation with normal goat serum. Sections were mounted inVectashield reagent (Vector Labs) and viewed on a Biorad 1024 ConfocalMicroscope.

For double labeling with a neural marker, animals of the genotype C155elav-Gal4; UAS-lacZ were sectioned and first hybridized with adigoxigenin labeled antisense DOR104 RNA probe and developed asdescribed above. Neuron-specific expression of lacZ driven by theelav-Gal4 enhancer trap was visualized with a polyclonal rabbitanti-β-galactosidase antibody (Organon-Technika/Cappel), visualized by agoat anti-rabbit Alexa488 conjugated secondary antibody (MolecularProbes) following preincubation with normal goat serum.

The proportion of neurons in the third antennal segment was calculatedby comparing the number of nuclei staining with the 44C11 ELAVmonoclonal (kindly provided by Lily Jan) and those staining with TOTO-3(Molecular Probes), a nucleic acid counterstain, in several confocalsections of multiple antennae. On average, 36% of the nuclei in theantenna were ELAV positive.

DOR104-lacZ Transgene Construction and Histochemical Staining

A genomic clone containing the DOR104 coding region and several kb ofupstream sequence was isolated from a genomic library prepared fromflies isogenic for the third chromosome (a gift of Kevin Moses and GerryRubin). Approximately 3 kb of DNA immediately upstream of the putativetranslation start site of DOR104 were isolated by PCR and subcloned intothe pCasperAUGβGal vector (Thummel et al., 1988). β-galactosidaseactivity staining was carried out with whole mount head preparationsessentially as described in Wang et al. (1998). Frozen sections ofDOR104-lacZ maxillary palps were incubated with a polyclonal rabbitanti-β-galactosidase antibody and as described above.

Experimental Results

Cloning Candidate Odorant Receptors

In initial experiments, a cDNA encoding a putative odorant receptor wasisolated by a difference cloning strategy designed to detect cDNA copiesof mRNA present at extremely low frequencies in an mRNA population. Inthe antenna and maxillary palp, about 30% of the cells are olfactoryneurons. If each neuron expressed only one of a possible 100 differentodorant receptor genes at a level of 0.1% of the mRNA in a sensoryneuron, then a given receptor mRNA would be encountered at a frequencyof one in 300,000 in antennal mRNA. If 100 different receptor genes wereexpressed, then the entire family of receptor genes would be representedat a frequency of one in 3,000 mRNAs. Experimental modifications weretherefore introduced into standard difference cloning to allow for theidentification of extremely rare mRNAs whose expression is restricted toeither the antenna or the maxillary palp.

Briefly, 5000 insets from an antennal/maxillary palp cDNA library wereprescreened (see Experimental Procedures) and then subjected to Southernblot hybridization with cDNA probes from antennal/maxillary palp, headminus antenna/maxillary palp, or virgin female body mRNA (see FIG. 1).This Southern blot hybridization (or reverse Northern) to candidatecDNAs allows for the detection of sequences present at a frequency of 1in 100,000 in the probe, a sensitivity about one hundred-fold greaterthan that of plaque screening (see Experimental Procedures). Thisprocedure led to the identification of multiple antennal/maxillarypalp-specific cDNAs that were analyzed by DNA sequencing and in situhybridization. One cDNA, DOR104 (for Drosophila Odorant Receptor) (SEQID NO: 3) (FIG. 1, Lane 9), encodes a putative seven-transmembranedomain protein (SEQ ID NO: 4) with no obvious sequence similarity toknown serpentine receptors (FIG. 3). In situ hybridization revealed thatthis cDNA anneals to about 15% of the 120 sensory neurons within themaxillary palp but does not anneal with neurons in either the brain orantenna. Seven cells expressing DOR104 are shown in the frontalmaxillary palp section in FIG. 2A.

These observations suggested that DOR104 might be one member of a largerfamily of odorant receptor genes within the Drosophila genome. However,additional genes homologous to DOR104 could not be identified by lowstringency hybridization to genomic DNA and cDNA libraries or uponanalysis of linked genes in a genomic walk. Therefore, the Drosophilagenome database was analyzed for families of multiple transmembranedomain proteins that share sequence similarity with DOR104. Sequencesrepresenting about 10% of the Drosophila genome were downloaded(Berkeley Drosophila Genome Project) and subjected to GENSCAN analysis(Burge and Karlin, 1997) to predict the intron-exon structure of allsequences within the database. Open reading frames greater than 50 aminoacids were searched for proteins with three or more predictedtransmembrane-spanning regions using the dense alignment surface (DAS)and TMAP algorithms (Persson and Argos, 1994; Cserzo et al., 1997; alsosee Experimental Procedures). Of 229 candidate genes identified in thismanner, 11 encode proteins that define a novel divergent family ofpresumed seven transmembrane domain proteins with sequence similarity tothe DOR104 sequence. This family of candidate odorant receptors does notshare any conserved sequence motifs with previously identified familiesof seven transmembrane domain receptors. cDNA clones containing thecoding regions for 5 of the 11 genes identified by GENSCAN analysis havebeen isolated from an antennal/maxillary palp cDNA library and theirsequences are provided in FIG. 3. The remaining 6 protein sequencesderive from GENSCAN predictions for intron-exon arrangement. Theirorganization conforms well to the actual structure determined from thecDNA sequences of other members of the gene family (FIG. 3).

The receptors consist of a short extracellular N-terminal domain(usually less than 50 amino acids) and seven presumed membrane-spanningdomains. Analysis of presumed transmembrane domains (Kyte and Doolittle,1982; Persson and Argos, 1994; Cserzo et al., 1997) reveals multiplehydrophobic segments, but it is not possible from this analysis tounequivocally determine either the number or placement of the membranespanning domains. At present, the assignment of transmembrane domains istherefore tentative.

The individual family members are divergent and most exhibit from 17-26%amino acid identity. Two linked clusters of receptor genes constitutesmall subfamilies of genes with significantly greater sequenceconservation. Two linked genes when expressed, DOR53 (SEQ ID NOs: 7 and8) and DOR67 (SEQ ID NOs: 9 and 10), exhibit 76% amino acid identity;whereas the three linked genes when expressed, DOR71g (SEQ ID NOs: 13and 14), DOR72g (SEQ ID NOs: 15 and 16) and DOR73g (SEQ ID Nos: 17 and18), reveal 30-55% identity (FIG. 3; see below). Despite the divergence,each of the genes shares short, common motifs in fixed positions withinthe putative seven transmembrane domain structure that define thesesequences as highly divergent members of a novel family of putativereceptor molecules.

Expression of the DOR Gene Family in Olfactory Neurons

If this gene family encodes putative odorant receptors in the fly, onemight expect that other members of the family in addition to DOR104would also be expressed in olfactory sensory neurons. Therefore, in situhybridization was performed to examine the pattern of receptorexpression of each of the 11 additional members of the gene family inadult and developing organisms. In Drosophila, olfactory sensory neuronsare restricted to the maxillary palp and third antennal segment. Thethird antennal segment is covered with approximately 500 fine sensorybristles or sensilla (Stocker, 1994), each containing from one to fourneurons (Venkatesh and Singh, 1984). The maxillary palp is covered withapproximately 60 sensilla, each of which is innervated by two or threeneurons (Singh and Nayak, 1985). Thus, the third antennal segment andmaxillary palp contain about 1500 and 120 sensory neurons, respectively.

RNA in situ hybridization experiments were performed withdigoxigenin-labeled RNA antisense probes to each of the 11 new membersof the gene family under conditions of high stringency. One linked pairof homologous genes, DOR53 and DOR67, crosshybridizes, whereas theremaining 10 genes exhibit no crosshybridization under these conditions(see below). Eight of the 11 genes hybridize to a small subpopulation(0.5-1.5%) of the 1500 olfactory sensory neurons in the third antennalsegment (FIG. 4). One gene, DOR71g, is expressed in about 10% of thesensory neurons in the maxillary palp but not in the antenna (FIG. 4G).Expression of DOR46 or DOR19g has not been detected in the antenna orthe maxillary palp. Expression of this gene family is only observed incells within the antenna and maxillary palp. No hybridization wasobserved in neurons of the brain, nor was hybridization observed in anysections elsewhere in the adult fly or in any tissue at any stage duringembryonic development. However, hybridization was observed to a smallnumber of cells in the developing antennae in the late pupal stage. Wehave not yet determined whether this family of receptors is expressed inthe larval olfactory apparatus.

Only about one third of the cells in the third antennal segment and themaxillary palp are neurons (data not shown), which are interspersed withnon-neuronal sensillar support cells and glia. Two experiments wereperformed to demonstrate that the family of seven transmembrane domainreceptor genes is expressed in sensory neurons rather than support cellsor glia within the antenna and maxillary palp. First, two-colorfluorescent antibody detection schemes were developed to co-localizereceptor expression in cells that express the neuron-specific RNAbinding protein, ELAV (Robinow and White, 1988). An enhancer trap linecarrying an insertion of GAL4 at the elav locus expresses high levels oflacZ in neurons when crossed to a transgenic UAS-lacZ responder line(Lin and Goodman, 1994). Fluorescent antibody detection of lacZidentifies the sensory neurons in a horizontal section of the maxillarypalp (FIG. 5B). Hybridization with the receptor probe DOR104 revealsexpression in 5 of the 12 lacZ positive cells in a horizontal section ofthe maxillary palp (FIG. 5A). All cells that express DOR104 are alsopositive for lacZ (FIG. 5C), indicating that this receptor is expressedonly in neurons.

In a second experiment, it was demonstrated that the receptor genes arenot expressed in non-neuronal cells. The support cells of the antennaexpress different members of a family of odorant binding proteins(McKenna et al., 1994; Pikielny et al., 1994; Kim et al., 1998). Thesegenes encode abundant low molecular weight proteins thought to transportodorants through the sensillar lymph (reviewed in Pelosi, 1994).Two-color in situ experiments with a probe for the odorant bindingprotein, PBPRP2 (Pikielny et al., 1994), reveal hybridization to a largenumber of cells broadly distributed throughout the antenna (FIG. 5F). Inthe same section, however, the probe DOR53 anneals to a non-overlappingsubpopulation of neurons restricted to the medial-proximal domain of theantenna. In a similar experiment, in situ hybridization with the odorantbinding protein, OS-F (McKenna et al., 1994), identifies a spatiallyrestricted subpopulation of support cells in the antenna, whereas theDOR67 probe identifies a distinct subpopulation of neurons in amedial-proximal domain (FIG. 5G). Thus, the putative odorant receptorgenes are expressed in a subpopulation of sensory neurons distinct fromthe support cells that express the odorant binding proteins. Takentogether, these data demonstrate that 10 of the 12 family membersdisclosed herein are expressed in small subpopulations of olfactorysensory neurons in the antenna and maxillary palp.

Spatially Defined Patterns of Receptor Expression

The in situ hybridization experiments reveal that each receptor isexpressed in a spatially restricted subpopulation of neurons in theantenna or maxillary palp (FIG. 4). The total number of cells expressingeach receptor per antenna was obtained by counting the positive cells inserial sections of antennae from multiple flies. These numbers arepresented in the legend of FIG. 4. DOR67 and 53 probes, for example,anneal to about 20 neurons on the medial proximal edge of the antenna(FIGS. 4A and B), whereas DOR62 and 87 probes anneal to subpopulationsof 20 cells at the distal edge of the antenna (FIG. 4C-D). Approximately10 cells in the distal domain express DOR64 (FIG. 4E). Each of the threelinked genes DOR71g, DOR72g, and DOR73g is expressed in differentneurons. DOR72g is expressed in approximately 15 antennal cells (FIG.4H), while DOR73g is expressed in 1 to 2 cells at the distal edge of theantenna (FIG. 4I). In contrast, DOR71g is expressed in approximately 10maxillary palp neurons but is not detected in the antenna (FIG. 4G). Thethree sensillar types are represented in a coarse topographic map acrossthe third antennal segment. The proximal-medial region, for example,contains largely basiconic sensilla. Receptors expressed in this region(DOR53 and 67) are therefore likely to be restricted to the largebasiconic sensilla. More distal regions contain a mixture of all threesensilla types and it is therefore not possible from these data toassign specific receptors to specific sensillar types.

The spatial pattern of neurons expressing a given receptor is conservedbetween individuals. In situ hybridization with two receptor probes tothree individual flies reveals that both the frequency and spatialdistributions of the hybridizing neurons is conserved in differentindividuals (FIG. 6). At present, the precision of this topographic mapcannot be determined and one can only argue that given receptors areexpressed in localized domains.

In preliminary experiments, the spatial pattern of expression of onereceptor, DOR104, was recapitulated in transgenic flies with a promoterfragment flanking the DOR104 gene. The fusion of the presumed DOR104promoter (consisting of 3 kb of 5′ DNA immediately adjacent to thecoding region) to the lacZ reporter gene has allowed us to visualize asubpopulation of neurons expressing DOR104 within the maxillary palp.Whole mount preparations of the heads of transgenic flies reveal a smallsubpopulation of sensory neurons within the maxillary palp whose cellbodies exhibit blue color after staining with X-gal (FIG. 2B). Thenumber of positive cells, approximately 20 per maxillary palp,corresponds well with that seen for DOR104 RNA expression.Immunofluorescent staining of sections with antibodies directed againstβ-galactosidase more clearly reveals the dendrites and axons of thesebipolar neurons in the maxillary palp (FIG. 2C). Levels of lacZexpression in these transgenic lines are low and further amplificationwill be necessary to allow us to trace the axons to glomeruli in theantennal lobe. Nonetheless, the data suggest that the informationgoverning the spatial pattern of DOR104 expression in a restrictedsubpopulation of maxillary palp neurons resides within 3 kb of DNA 5′ tothe DOR104 gene.

Individual Neurons Express Different Complements of Receptors

An understanding of the logic of olfactory discrimination in Drosophilawill require a determination of the diversity and specificity ofreceptor expression in individual neurons. In the vertebrate olfactoryepithelium, a given neuron is likely to express only one receptor fromthe family of 1,000 genes (Ngai et al., 1993; Ressler et al., 1993;Vassar et al., 1993; Chess et al., 1994). In the nematode C. elegans,however, individual chemosensory neurons are thought to express multiplereceptor genes (Troemel et al., 1995). Our observations with theputative Drosophila odorant receptors indicate that a given receptorprobe anneals with 0.5-1.5% of antennal neurons, suggesting that eachcell expresses only a subset of receptor genes. If we demonstrate thateach of the different receptor probes hybridizes with distinct,nonoverlapping subpopulations of neurons, this would provide evidencethat neurons differ with respect to the receptors they express.

In situ hybridization was therefore performed with either a mix of fivereceptor probes (FIG. 4F) or individually with each of the five probes(FIG. 4A-E). The number of olfactory neurons identified with the mixedprobe (about 60 per antenna) approximates the sum of the positiveneurons detected with the five individual probes. These resultsdemonstrate that individual receptors are expressed in distinctnonoverlapping populations of olfactory neurons.

An additional experiment was performed using two-color RNA in situhybridization to ask whether two receptor genes, DOR64 and DOR87,expressed in interspersed cells in the distal antenna are expressed indifferent neurons. Antisense RNA probes for the two genes were labeledwith either digoxigenin- or FITC-UTP and were used in pairwisecombinations in in situ hybridization to sections through the Drosophilaantenna. Although these two genes are expressed in overlappinglateral-distal domains, two-color in situ hybridization reveals thatneurons expressing DOR64 do not express DOR87, rather each gene isexpressed in distinct cell populations (FIGS. 5D and E). Taken together,these data suggest that olfactory sensory neurons within the antenna arefunctionally distinct and express different complements of odorantreceptors. At the extreme, the experiments are consistent with a modelin which individual neurons express only a single receptor gene.

Our differential cloning procedure identified one additional gene,DORA45 (SEQ ID NOs: 103 and 104), which shares weak identity (24%) withthe DOR gene family over a short region (93 amino acids). This gene,however, does not appear to be a classical member of the DOR family: itis far more divergent and significantly larger than the other familymembers (486 amino acids). This gene is expressed in all olfactorysensory neurons. If DORA45 does encode a divergent odorant receptor,then it would be present in all sensory neurons along with differentcomplements of the more classical members of the DOR gene family.

The Size and Organization of the Odorant Receptor Gene Family

How large is the family of odorant receptor genes in Drosophila? Unlikevertebrate odorant receptors, which share 40-98% sequence identity atthe amino acid level, the fly receptors are extremely divergent. Theextent of sequence similarity between receptor subfamilies ranges from20-30%. The maxillary palp receptor DOR104 is the most distantly relatedmember of the family with about 17% identity to the other receptorgenes. Inspection of the receptor sequences suggests that Southern blothybridizations, even those performed at low stringency, are unlikely toreveal multiple additional members of a gene family. In accord withthis, Southern blot hybridization with receptor probes for DOR24, DOR62,and DOR72g, performed at either high or low stringency, reveals only asingle hybridizing band following cleavage of genomic DNA with threedifferent restriction endonucleases (FIG. 7C-E). The two linked clustersof receptors contain genes with a greater degree of sequenceconservation and define small subfamilies of receptor genes. A clusterof three receptors, DOR71g, DOR72g, and DOR73g, is located at mapposition 33B1-2. The antennal receptors DOR72g and DOR73g are 55%identical and both exhibit about 30% identity to the third gene at thelocus, DOR71g, which is expressed in the maxillary palp. DOR67 andDOR53, members of a second subfamily, reside within 1 kb of each otherat map position 22A2-3 and exhibit 76% sequence identity. Notsurprisingly, these two linked genes crosshybridize at low stringency.Southern blots with either DOR67 or DOR53 probes reveal two hybridizingbands corresponding to the two genes within the subfamily but fail todetect additional subfamily members in the chromosome (FIGS. 7A and B).

The members of the receptor gene family described here are present onall but the small fourth chromosome. No bias is observed towardtelomeric or centromeric regions. The map positions, as determined fromP1 and cosmid clones (Berkeley Drosophila Genome Project; EuropeanDrosophila Genome Project) are provided in Experimental Procedures. Acomparatively large number of receptor genes map to chromosome 2 becausethe Berkeley Drosophila Genome Project has concentrated its efforts onthis chromosome. Unlike the distribution of odorant receptors innematodes and mammals (Ben-Arie et al., 1994; Troemel et al., 1995;Robertson, 1998), only small linked arrays have been identified and themajority of the family members are isolated at multiple, scattered lociin the Drosophila genome.

The high degree of divergence among members of the Drosophila odorantreceptor gene family is more reminiscent of the family of chemoreceptorsin C. elegans than the more highly conserved odorant receptors ofvertebrates. Estimates of the size of the Drosophila receptor genefamily, therefore, cannot be obtained by either Southern blothybridization or PCR analysis of genomic DNA. Rather, estimates of thegene family derive from the statistics of small numbers. Twelve membersof the odorant receptor gene family were detected from a Drosophilagenome database that includes roughly 10% of the genome. Recognizing apossible bias in this estimate, it seems reasonable at present toestimate that the odorant receptor family is likely to include 100 to200 genes. This is in accord with independent estimates from in situhybridization experiments that demonstrate that a given receptor probehybridizes with 0.5-1.5% of the neurons. If one assumes that a givenneuron expresses only a single receptor gene, these observations suggestthat the gene family would include 100 to 200 members.

Experimental Discussion

The Size and Divergence of the Gene Family

The present application discloses a novel family of seven transmembranedomain proteins that is likely to encode the Drosophila odorantreceptors. The number of different receptor genes expressed in theneurons of the antenna and maxillary palp will reflect the diversity andspecificity of odor recognition in the fruit fly. How large is theDrosophila odorant receptor gene family? We have identified 11 membersof this divergent gene family in the Drosophila DNA database. Thepotential for bias notwithstanding, it seems reasonable to assume thenthat since only 10% of genomic sequence has been deposited, this genefamily is likely to contain from 100 to 200 genes. However, significanterrors in these estimates could result from bias in the nature of thesequences represented in the 10% of the Drosophila genome analyzed todate. In situ hybridization experiments demonstrating that each of thereceptor genes labels from 0.5-1.5% of the olfactory sensory neurons arein accord with the estimate of 100 to 200 receptor genes.

Several divergent odorant receptor gene families, each encoding seventransmembrane proteins, have been identified in vertebrate andinvertebrate species. In mammals, volatile odorants are detected by afamily of as many as 1,000 receptors each expressed in the mainolfactory epithelium (Buck and Axel, 1991; Levy et al., 1991; Parmentieret al., 1992; Ben-Arie et al., 1994). This gene family shares featureswith the serpentine neurotransmitter receptors and is conserved in allvertebrates examined. Terrestrial vertebrates have a second anatomicallyand functionally distinct olfactory system, the vomeronasal organ,dedicated to the detection of pheromones. Vomeronasal sensory neuronsexpress two distinct families of receptors each thought to contain from100 to 200 genes: one novel family of serpentine receptors (Dulac andAxel, 1995), and a second related to the metabotropic neurotransmitterreceptors (Herrada and Dulac, 1997; Matsunami and Buck, 1997; Ryba andTirindelli, 1997).

In the invertebrate C. elegans, chemosensory receptors are organizedinto four gene families that share 20-40% sequence similarity within afamily and essentially no sequence similarity between families (Troemelet al., 1995; Sengupta et al., 1996; Robertson, 1998). The four genefamilies in C. elegans together contain about 1,000 genes engaged in thedetection of odors. The nematode receptors exhibit no sequenceconservation with the three distinct families of vertebrate odorantreceptor genes. Our studies reveal that Drosophila has evolved anadditional divergent gene family of serpentine receptors comprised offrom 100 to 200 genes.

The observation that a similar function, chemosensory detection, isaccomplished by at least eight highly divergent gene families, sharinglittle or no sequence similarity, is quite unusual.

Why is the evolutionary requirement for odorant receptors so often metby recruitment of novel gene families rather than exploitingpre-existing odorant receptor families in ancestral genomes? Thecharacter of natural odorants along with their physical properties (e.g.aqueous or volatile) represent important selectors governing theevolution of receptor gene families. The use of common “anthropomorphic”odorant sets in the experimental analysis of olfactory specificity hasled to the prevailing view that significant overlap exists in therepertoire of perceived odors between different species. Studies ofodorant specificity in different species often employ odors atartificially high concentrations and may present an inaccurate image ofthe natural repertoire of odorants. We simply do not know the nature ofthe odors that initially led to the ancestral choice of receptor genesduring the evolution of the nematode, insect, or vertebrate species.Clearly, vastly different properties in salient odors could dictate therecruitment of new gene families to effect an old function, olfaction.The character of the odor is not the only evolutionary selector. Odorantreceptors must interact with other components in the signal transductionpathway [G proteins (for review see Buck, 1996; Bargmann and Kaplan,1998) and perhaps even RAMPs (McLatchie et al, 1998) and rho (Mitchellet al., 1998)] that may govern the choice of one family of serpentinereceptors over another. Moreover, mammalian receptors not only recognizeodorants in the environment but are likely to recognize guidance cuesgoverning formation of a sensory map in the brain (Wang et al., 1998).Thus, the multiple properties required of the odorant receptors mightchange vastly over evolutionary time and this might underlie theindependent origins of the multiple chemosensory receptor gene families.

Establishing a Topographic Map in the Antenna and the Brain

Individual receptor genes in the fly are expressed in topographicallyconserved domains within the antenna. This highly ordered spatialdistribution of receptor expression differs from that observed in themammalian olfactory epithelium. In mammals, a given receptor can beexpressed in one of four broad but circumscribed zones in the mainolfactory epithelium (Ressler et al., 1993; Vassar et al., 1993). Agiven zone can express up to 250 different receptors and neuronsexpressing a given receptor within a zone appear to be randomlydispersed (Ressler et al., 1993; Vassar et al., 1993). The highlyordered pattern of expression observed in the Drosophila antenna mighthave important implications for patterning the projections to theantennal lobe. In visual, somatosensory, and auditory systems theperipheral receptor sheet is highly ordered and neighbor relations inthe periphery are maintained in the projections to the brain. Theseobservations suggest that the relative position of the sensory neuron inthe periphery will determine the pattern of projections to the brain.

Our data on the spatial conservation of receptor expression in theantenna suggest that superimposed upon coarse spatial patterning ofolfactory sensilla (Venkatesh and Singh, 1984; Ray and Rodrigues, 1995;Reddy et al., 1997) must be more precise positional informationgoverning the choice of receptor expression. This spatial informationmight dictate the fixed topographic pattern of receptor expression inthe peripheral receptor sheet and at the same time govern the orderedsensory projections to the brain. This relationship between positionalidentity and the pattern of neuronal projections has been suggested forboth peripheral sensory neurons (Merritt and Whitington, 1995;Grillenzoni et al., 1998) and neurons in the embryonic central nervoussystem of Drosophila (Doe and Skeath, 1996).

Implications for Sensory Processing

In mammals, olfactory neurons express only one of the thousand odorantreceptor genes. Neurons expressing a given receptor project withprecision to 2 of the 1800 glomeruli in the mouse olfactory bulb.Odorants will therefore elicit spatially defined patterns of glomerularactivity such that the quality of an olfactory stimulus is encoded bythe activation of a specific combination of glomeruli (Stewart et al.,1979; Lancet et al., 1982; Kauer et al., 1987; Imamura et al., 1992;Mori et al., 1992; Katoh et al., 1993; Friedrich and Korsching, 1997).Moreover, the ability of an odorant to activate a combination ofglomeruli allows for the discrimination of a diverse array of odors farexceeding the number of receptors and their associated glomeruli. In thenematode, an equally large family of receptor genes is expressed in 16pairs of chemosensory cells, only three of which respond to volatileodorants (Bargmann and Horvitz, 1991; Bargmann et al., 1993). Thisimmediately implies that a given chemosensory neuron will expressmultiple receptors and that the diversity of odors recognized by thenematode might approach that of mammals, but the discriminatory power isnecessarily dramatically reduced.

What does the character of the gene family identified herein inDrosophila tell us about the logic of olfactory processing in thisorganism? We estimate that the Drosophila odorant receptors comprise afamily of from 100 to 200 genes. Moreover, the pattern of expression ofthese genes in the third antennal segment suggests that individualsensory neurons express a different complement of receptors and, at theextreme, the data presented herein are consistent with the suggestionthat individual neurons express one or a small number of receptors. Asin the case of mammals, the problem of odor discrimination thereforereduces to a problem of the brain discerning which receptors have beenactivated by a given odorant. If the number of different types ofneurons exceeds the number of glomeruli (43) (Stocker, 1994; Laissue etal., 1999), it immediately follows that a given glomerulus must receiveinput from more than one kind of sensory neuron. This implies that asingle glomerulus will integrate multiple olfactory stimuli. Onepossible consequence of this model would be a loss of discriminatorypower while maintaining the ability to recognize a vast array of odors.Alternatively, significant processing of sensory input may occur in thefly antennal lobe to afford discrimination commensurate with the largenumber of receptors.

This model of olfactory coding is in sharp contrast with the mainolfactory system of vertebrates in which sensory neurons express only asingle receptor and converge on only a single pair of spatially fixedglomeruli in the olfactory bulb. Moreover, each projection neuron in themammalian bulb extends its dendrite to only a single glomerulus. Thusthe integration and decoding of spatial patterns of glomerular activity,in vertebrates, must occur largely in the olfactory cortex. In the fruitfly, the observation that the number of receptors may exceed the numberof glomeruli suggests that individual glomeruli will receive input frommore than one type of sensory neuron. A second level of integration inthe antennal lobe is afforded by subsets of projection neurons thatelaborate extensive dendritic arbors that synapse with multipleglomeruli. Thus, the Drosophila olfactory system reveals levels ofprocessing and integration of sensory input in the antennal lobe that islikely to be restricted to higher cortical centers in the main olfactorysystem of vertebrates.

Protein and Nucleic Acid (nt) Sequences of 55 Drosophila OdorantReceptor Genes

The following includes those genes first identified in 1998-1999.Protein sequences used single letter amino acid codes. DOR10 (SEQ ID NO:26) MEKLRSYEDFIFMANMMFKTLGYDLFHTPKPWWRYLLVRGYFVLCTISNFYEASMVTTRIIEWESLAGSPSKIMRQGLHFFYMLSSQLKFITFMINRKRLLQLSHRLKELYPHKEQNQRKYEVNKYYLSCSTRNVLYVYYFVMVVMALEPLVQSQFIVNVSLGTDLWMMCVSSQISMHLGYLANMLASIRPSPETEQQDCDFLASIIKRHQLMIRLQKDVNYVFGLLLASNLFTTSCLLCCMAYYTVVEGFNWEGISYMMLFASVAAQFYVVSSHGQMLIDLLMTITYRFFAVIRQTVEK DOR10nt (SEQ ID NO:25) ATGGAAAAACTACGTTCCTATGAGGATTTCATCTTCATGGCCAACATGATGTTCAAGACCCTTGGCTACGATCTATTCCATACACCCAAACCCTGGTGGCGCTATCTGCTTGTGCGAGGATACTTCGTTTTGTGCACGATCAGCAACTTTTACGAGGCTTCCATGGTGACGACAAGGATAATTGAGTGGGAATCCTTGGCCGGAAGTCCCTCCAAAATAATGCGACAGGGTCTGCACTTCTTTTACATGTTGAGTAGCCAATTGAAATTTATCACATTCATGATAAATCGCAAACGCCTACTGCAGCTGAGCCATCGTTTGAAAGAGTTGTATCCTCATAAAGAGCAAAATCAAAGGAAGTACGAGGTGAATAAATACTACCTATCCTGTTCCACGCGCAATGTTTTGTACGTGTACTACTTTGTAATGGTCGTCATGGCACTGGAACCCCTCGTTCAGTCCCAGTTCATAGTGAATGTGAGCCTGGGCACAGATCTGTGGATGATGTGCGTCTCAAGCCAAATATCGATGCACTTGGGCTATCTGGCCAATATGTTGGCCTCCATTCGACCAAGTCCAGAAACGGAACAACAAGACTGTGACTTCTTGGCCAGCATTATAAAGAGACATCAACTAATGATCAGGCTTCAAAAGGACGTGAACTATGTTTTTGGACTCTTATTGGCATCTAATCTGTTTACCACATCCTGTTTACTTTGCTGCATGGCGTACTATACCGTCGTCGAAGGTTTCAATTGGGAGGGCATTTCCTATATGATGCTCTTTGCTAGTGTAGCTGCCCAGTTCTACGTTGTCAGCTCACACGGACAAATGTTAATAGATTTGTTGATGACCATCACATACAGATTTTTCGCGGTTATACGACAAACTGTAGAAAAG DOR104 (SEQ ID NO: 4)MASLQFHGNVDADIRYDISLDPARESNLFRLLMGLQLANGTKPSPRLPKWWPKRLEMIGKVLPKAYCSMVIFTSLHLGVLFTKTTLDVLPTGELQAITDALTMTIIYFFTGYGTIYWCLRSRRLLAYMEHMNREYRHHSLAGVTFVSSHAAFRMSRNFTVVWIMSCLLGVISWGVSPLMLGIRMLPLQCWYPFDALGPGTYTAVYATQLFGQIMVGMTFGFGGSLFVTLSLLLLGQFDVLYCSLKNLDAHTKLLGGESVNGLSSLQEELLLGDSKRELNQYVLLQEHPTDLLRLSAGRKCPDQGNAFHNALVECIRLHRFILHCSQELENLFSPYCLVKSLQITFQLCLLVFVGVSGTREVLRIVNQLQYLGLTIFELLMFTYCGELLSRHSIRSGDAFWRGAWWKHAHFIRQDILIFLVNSRRAVHVTAGKFYVMDVNRLRSVITQAFS FLTLLQKLAAKKTESELDOR104nt (SEQ ID NO: 3)GAATTCGGCACGAGCAGTCGATGGCCAGTCTTCAGTTCCACGGCAACGTCGATGCGGACATCAGGTATGATATTAGCCTGGATCCGGCTAGGGAATCGAATCTCTTCCGTCTGCTAATGGGACTCCAGTTGGCGAATGGCACGAAGCCATCGCCGCGGTTACCCAAATGGTGGCCAAAGCGGCTGGAAATGATTGGTAAAGTGCTGCCCAAAGCCTATTGTTCCATGGTGATTTTCACCTCCCTGCATTTGGGTGTCCTGTTCACGAAAACCACACTGGATGTCCTGCCGACGGGGGAGCTGCAGGCCATAACGGATGCCCTCACCATGACCATAATATACTTTTTCACGGGCTACGGCACCATCTACTGGTGCCTGCGCTCCCGGCGCCTCTTGGCCTACATGGAGCACATGAACCGGGAGTATCGCCATCATTCGCTGGCCGGGGTGACCTTTGTGAGTAGCCATGCGGCCTTTAGGATGTCCAGAAACTTCACGGTGGTGTGGATAATGTCCTGCCTGCTGGGCGTGATTTCCTGGGGCGTTTCGCCACTGATGCTGGGCATCCGGATGCTGCCGCTCCAATGTTGGTATCCCTTCGACGCCCTGGGTCCCGGCACATATACGGCGGTCTATGCTACACAACTTTTCGGTCAGATCATGGTGGGCATGACCTTTGGATTCGGGGGATCACTGTTTGTCACCCTGAGCCTGCTACTCCTGGGACAATTCGATGTGCTCTACTGCAGCCTGAAGAACCTGGATGCCCATACCAAGTTGCTGGGCGGGGAGTCTGTAAATGGCCTGAGTTCGCTGCAAGAGGAGTTGCTGCTGGGGGACTCGAAGAGGGAATTAAATCAGTACGTTTTGCTCCAGGAGCATCCGACGGATCTGCTGAGATTGTCGGCAGGACGAAAATGTCCTGACCAAGGAAATGCGTTTCACAACGCCTTGGTGGAATGCATTCGCTTGCATCGCTTCATTCTGCACTGCTCACAGGAGTTGGAGAATCTATTCAGTCCATATTGTCTGGTCAAGTCACTGCAGATCACCTTTCAGCTTTGCCTGCTGGTCTTTGTGGGCGTTTCGGGTACTCGAGAGGTCCTGCGGATTGTCAACCAGCTACAGTACTTGGGACTGACCATCTTCGAGCTCCTAATGTTCACCTATTGTGGCGAACTCCTCAGTCGGCATAGTATTCGATCTGGCGACGCCTTTTGGAGGGGTGCGTGGTGGAAGCACGCCCATTTCATCCGCCAGGACATCCTCATCTTTCTGGTCAATAGTAGACGTGCAGTTCACGTGACTGCCGGCAAGTTTTATGTGATGGATGTGAATCGTCTAAGATCGGTTATAACGCAGGCGTTCAGCTTCTTGACTTTGCTGCAAAAGTTGGCTGCCAAGAAGACGGAATCGGAGCTCTAAACTGGTACCACGCATCGATATTTATTTAGCGCATTAAAAAAAAGTCGAGTAAAAGCAAAAAAAAAAAAAAAAAAA DOR105 (SEQ ID NO: 28)MFEDIQLIYMNIKILRFWALLYDKNLRRYVCIGLASFHIFTQIVYMMSTNEGLTGIIRNSYMLVLWINTVLRAYLLLADHDRYLALIQKLTEAYYDLLNLNDSYISEILDQVNKVGKLMARGNLFFGMLTSMGFGLYPLSSSERVLPFGSKIPGLNEYESPYYEMWYIFQMLITPMGCCMYIPYTSLIVGLIMFGIVRCKALQHRLRQVALKHPYGDRDPRELREEIIACIRYQQSIIEYMDHINELTTMMFLFELMAFSALLCALLFMLIIVSGTSQLIIVCMYINMILAQILALYWYANELREQNLAVATAAYETEWFTFDVPLRKNILFMMMRAQRPAAILLGNIRPITLELFQNLLNTTYTFFTVLKRVYG DOR105nt (SEQ ID NO: 27)ATGTTTGAAGACATTCAGCTAATCTACATGAATATCAAGATATTGCGATTCTGGGCCCTGCTCTATGACAAAAACTTGAGGCGTTATGTGTGCATTGGACTGGCCTCATTCCACATCTTCACCCAAATCGTCTACATGATGAGTACCAATGAAGGACTAACCGGGATAATTCGTAACTCATATATGCTCGTCCTTTGGATTAATACGGTGCTGCGAGCTTATCTCTTGCTGGCGGATCACGACAGATATTTGGCTTTGATCCAAAAACTAACTGAGGCCTATTACGATTTACTGAATCTGAACGATTCGTATATATCGGAAATATTGGACCAGGTGAACAAGGTGGGAAAGTTGATGGCTAGGGGCAATCTGTTCTTTGGCATGCTCACATCCATGGGATTCGGTCTGTACCCATTGTCCTCCAGCGAAAGAGTCCTGCCATTTGGCAGCAAAATTCCTGGTCTAAATGAGTACGAGAGTCCGTACTATGAGATGTGGTACATCTTTCAGATGCTCATCACCCCGATGGGCTGTTGCATGTACATTCCGTACACCAGTCTGATTGTGGGCTTGATAATGTTCGGCATTGTGAGGTGCAAGGCTTTGCAGCATCGCCTCCGCCAGGTGGCGCTTAAGCATCCGTACGGAGATCGCGATCCCCGTGAACTGAGGGAGGAGATCATAGCCTGCATACGTTACCAGCAGAGCATTATCGAGTACATGGATCACATAAACGAGCTGACCACCATGATGTTCCTATTCGAACTGATGGCCTTTTCGGCGCTGCTCTGTGCGCTGCTCTTTATGCTGATTATCGTCAGCGGCACCAGTCAGCTGATAATTGTTTGCATGTACATTAACATGATTCTGGCCCAAATACTGGCCCTCTATTGGTATGCAAATGAGTTAAGGGAACAGAATCTGGCGGTGGCCACCGCAGCCTACGAAACGGAGTGGTTCACCTTCGACGTTCCACTGCGCAAAAACATCCTGTTCATGATGATGAGGGCACAGCGGCCAGCTGCAATACTACTGGGCAATATACGCCCCATCACTTTGGAACTGTTCCAAAACCTACTGAACACAACCTATACATTTTTTACGGTTCTCAAGCGAGTCTACGGA DOR107 (SEQ ID NO: 30)MYPRFLSRNYPLAKHLFFVTRYSFGLLGLRFGKEQSWLHLLWLVFNFVNLAHCCQAEFVFGWSHLRTSPVDAMDAFCPLACSFTTLFKLGWMWWRRQEVADLMDRIRLLIGEQEKREDSRRKVAQRSYYLMVTRCGMLVFTLGSITTGAFVLRSLWEMWVRRHQEFKFDMPFRMLFHDFAHRMPWFPVFYLYSTWSGQVTVYAFAGTDGFFFGFTLYMAFLLQALRYDIQDALKPIRDPSLRESKICCQRLADIVDRHNEIEKIVKEFSGIMAAPTFVHFVSASLVIATSVIDILLYSGYNIIRYVVYTFTVSSAIFLYCYGGTEMSTESLSLGEAAYSSAWYTWDRETRRRVFLIILRAQRPITVRVPFFAPSLPVFTSVIKFTGSIVALAKTIL DOR107nt (SEQ ID NO: 29)ATGTATCCGCGATTCCTCAGCCGTAACTATCCGCTGGCCAAGCATTTGTTCTTCGTCACCAGATACTCCTTTGGCCTGCTGGGCCTGAGATTTGGCAAAGAGCAATCGTGGCTTCACCTCTTGTGGCTGGTGTTCAATTTCGTTAACCTGGCGCACTGCTGCCAGGCGGAGTTCGTCTTCGGCTGGAGTCACTTGCGCACCAGTCCCGTGGATGCCATGGACGCCTTTTGTCCTCTGGCCTGCAGTTTCACCACGCTCTTCAAGCTGGGATGGATGTGGTGGCGTCGCCAGGAAGTAGCTGATCTAATGGACCGCATCCGCTTGCTCATCGGGGAGCAGGAGAAGAGGGAGGACTCCCGGAGAAAGGTGGCTCAAAGGAGCTACTATCTCATGGTCACCAGGTGCGGTATGCTGGTCTTCACCCTGGGCAGCATTACCACTGGAGCCTTCGTTCTGCGTTCCCTTTGGGAAATGTGGGTGCGTCGTCATCAGGAGTTCAAATTCGATATGCCCTTTCGCATGCTGTTCCACGACTTTGCGCATCGCATGCCCTGGTTTCCAGTTTTCTATCTCTACTCCACATGGAGTGGCCAGGTCACTGTGTACGCCTTTGCTGGTACAGATGGTTTCTTCTTTGGCTTTACCCTCTACATGGCCTTCTTGCTGCAGGCCTTAAGATACGATATCCAGGATGCCCTCAAGCCAATAAGAGATCCCTCGCTTAGGGAATCCAAAATCTGCTGTCAGCGATTGGCGGACATCGTGGATCGCCACAATGAGATAGAGAAGATAGTCAAGGAATTTTCTGGAATTATGGCTGCTCCAACTTTTGTTCACTTCGTATCAGCCAGCTTAGTGATAGCCACCAGCGTCATTGATATACTATTGTATTCCGGCTATAACATCATCCGTTACGTGGTGTACACCTTCACGGTTTCCTCGGCCATCTTCCTCTATTGCTACGGAGGCACAGAAATGTCAACTGAGAGCCTTTCCTTGGGAGAAGCAGCCTACAGCAGTGCCTGGTATACTTGGGATCGAGAGACCCGCAGGCGGGTCTTTCTCATTATCCTGCGTGCTCAACGACCCATTACGGTGAGGGTGCCCTTTTTTGCACCATCGTTACCAGTCTTCACATCGGTCATCAAGTTTACAGGTTCGATTGTGGCACTGGCTAAGACGATACTG DOR108 (SEQ ID NO: 32)MDKHKDRIESMRLILQVMQLFGLWPWSLKSEEEWTFTGFVKRNYRFLLHLPITFTFIGLMWLEAFISSNLEQAGQVLYMSITEMALVVKILSIWHYRTEAWRLMYELQHAPDYQLHNQEEVDFWRREQRFFKWFFYIYILlSLGVVYSGCTGVLFLEGYELPFAYYVPFEWQNERRYWFAYGYDMAGMTLTCISNITLDTLGCYFLFHISLLYRLLGLRLRETKNMKNDTIFGQQLRAIFIMHQRIRSLTLTCQRIVSPYILSQIILSALIICFSGYRLQHVGIRDNPGQFISMLQFVSVMILQIYLPCYYGNEITVYANQLTNEVYHTNWLECRPPIRKLLNAYMEHLKKPVTIRAGNSFAVGLPIFVKTINNAYSFLALLLNVSN DOR108nt (SEQ ID NO: 31)ATGGATAAACACAAGGATCGCATTGAATCCATGCGCCTAATTCTTCAGGTCATGCAACTATTTGGCCTCTGGCCGTGGTCCTTGAAATCGGAAGAGGAGTGGACTTTCACCGGTTTTGTAAAGCGCAACTATCGCTTCCTCCTCCATCTGCCCATTACCTTCACCTTTATTGGACTCATGTGGCTGGAGGCCTTCATCTCGAGCAATCTGGAGCAGGCTGGCCAGGTTCTGTACATGTCCATCACCGAGATGGCTTTGGTGGTGAAAATCCTGAGCATTTGGCACTATCGCACCGAAGCTTGGCGGCTGATGTACGAACTCCAACATGCTCCGGACTACCAACTCCACAACCAGGAGGAGGTAGACTTTTGGCGCCGGGAGCAACGATTCTTCAAGTGGTTCTTCTACATCTACATTCTGATTAGCTTGGGCGTGGTATATAGTGGCTGCACTGGAGTACTTTTTCTGGAGGGCTACGAACTGCCCTTTGCCTACTACGTGCCCTTCGAATGGCAGAACGAGAGAAGGTACTGGTTCGCCTATGGTTACGATATGGCGGGCATGACGCTGACCTGCATCTCAAACATTACCCTGGACACCCTGGGTTGCTATTTCCTGTTCCATATCTCTCTTTTGTACCGACTGCTTGGTCTGCGATTGAGGGAAACGAAGAATATGAAGAATGATACCATTTTTGGCCAGCAGTTGCGTGCCATCTTCATTATGCATCAGAGGATTAGAAGCCTAACCCTGACCTGCCAGAGAATCGTATCTCCCTATATCCTATCTCAGATCATTTTGAGTGCCCTGATCATCTGCTTTAGTGGATACCGCTTGCAGCATGTGGGAATTCGCGATAATCCCGGCCAGTTTATATCCATGTTGCAGTTTGTCAGTGTGATGATCCTGCAGATTTACTTGCCCTGCTACTATGGAAACGAGATAACCGTGTATGCCAATCAGCTGACCAACGAGGTTTACCATACCAATTGGCTGGAATGTCGGCCACCGATTCGAAAGTTACTCAATGCCTACATGGAGCACCTGAAGAAACCGGTGACCATCCGGGCTGGCAACTCCTTCGCCGTGGGACTACCAATTTTTGTTAAGACCATCAACAACGCCTACAGTTTCTTGGCTTTATTACTAA ATGTATCGAAT DOR109(SEQ ID NO: 34) MESTNRLSAIQTLLVIQRWIGLLKWENEGEDGVLTWLKRIYPFVLHLPLTFTYIALMWYEAITSSDFEEAGQVLYMSITELALVTKLLNIWYRRHEAASLIHELQHDPAFNLRNSEEIKFWQQNQRNFKRIFYWYIWGSLFVAVMGYISVFFQEDYELPFGYYVPFEWRTRERYFYAWGYNVVAMTLCCLSNILLDTLGCYFMFHIASLFRLLGMRLEALKNAAEEKARPELRRIFQLHTKVRRLTRECEVLVSPYVLSQVVFSAFIICFSAYRLVHMGFKQRPGLFVTTVQFVAVMIVQIFLPCYYGNELTFHANALTNSVFGTNWLEYSVGTRKLLNCYMEFLKRPVKVRAGVFFEIGLPIFVKTINNAYSFFALLLKISK DOR109nt (SEQ ID NO: 33)ATGGAGTCTACAAATCGCCTAAGTGCCATCCAAACACTTTTAGTAATCCAACGTTGGATAGGACTTCTTAAATGGGAAAACGAGGGCGAGGATGGAGTATTAACCTGGCTAAAACGAATATATCCTTTTGTACTGCACCTTCCACTGACCTTCACGTATATTGCCTTAATGTGGTATGAAGCTATTACATCGTCAGATTTTGAGGAAGCTGGTCAAGTTCTGTACATGTCCATCACCGAACTGGCATTGGTCACTAAACTGCTGAATATTTGGTATCGTCGTCATGAAGCTGCTAGTCTAATCCACGAATTGCAACACGATCCCGCATTTAATCTGCGCAATTCGGAGGAAATCAAATTCTGGCAGCAAAATCAGAGGAACTTTAAGAGAATATTTTACTGGTACATCTGGGGCAGCCTTTTCGTGGCTGTAATGGGTTATATAAGCGTGTTTTTCCAGGAGGATTACGAGCTGCCCTTTGGCTACTACGTGCCATTCGAGTGGCGCACCAGGGAACGATACTTCTACGCTTGGGGCTATAATGTGGTGGCCATGACCCTGTGCTGTCTATCCAACATCCTACTGGACACACTAGGCTGTTATTTCATGTTCCACATCGCCTCGCTTTTCAGGCTTTTGGGAATGCGACTGGAGGCCTTGAAAAATGCAGCCGAAGAGAAAGCCAGACCGGAGTTGCGCCGCATTTTCCAACTGCACACTAAAGTCCGCCGATTGACGAGGGAATGCGAAGTGTTAGTTTCACCCTATGTTCTATCCCAAGTGGTCTTCAGTGCCTTCATCATCTGCTTCAGTGCCTATCGACTGGTGCACATGGGCTTCAAGCAGCGACCTGGACTCTTCGTGACCACCGTGCAATTCGTGGCCGTCATGATCGTCCAGATTTTCTTGCCCTGTTACTACGGCAATGAGTTGACCTTTCATGCCAATGCACTCACTAATAGTGTCTTCGGTACCAATTGGCTGGAGTACTCCGTGGGCACTCGCAAGCTGCTTAACTGCTACATGGAGTTCCTCAAGCGACCGGTTAAAGTGCGAGCTGGGGTGTTCTTTGAAATAGGACTACCCATCTTTGTGAAGACCATCAACAATGCCTACAGTTTCTTCGCCCTGCTGCTAAAGATATCCAAG DOR110 (SEQ ID NO: 36)MLFNYLRKPNPTNLLTSPDSFRYFEYGMFCMGWHTPATHKIIYYITSCLIFAWCAVYLPIGIIISFKTDINTFTPNELLTVMQLFFNSVGMPFKVLFFNLYISGFYKAKKLLSEMDKRCTTLKERVEVHQGVVRCNKAYLIYQFIYTAYTISTFLSAALSGKLPWRIYNPFVDFRESRSSFWKAALNETALMLFAVTQTLMSDIYPLLYGLILRVHLKLLRLRVESLCTDSGKSDAENEQDLINYAAAIRPAVTRTIFVQFLLIGICLGLSMINLLFFADIWTGLATVAYINGLMVQTFPFCFVCDLLKKDCELLVSAIFHSNWINSSRSYKSSLRYFLKNAQKSIAFTAGSIFPISTGSNIKVAKLAFSVVTFVNQLNIADRLTKN DOR110nt (SEQ ID NO: 35)ATGTTGTTCAACTATCTGCGAAAGCCGAATCCCACAAACCTTTTGACTTCTCCGGACTCATTTAGATACTTTGAGTATGGAATGTTTTGCATGGGATGGCACACACCAGCAACGCATAAGATAATCTACTATATAACATCCTGTTTGATTTTTGCTTGGTGTGCCGTATACTTGCCAATCGGAATCATCATTAGTTTCAAAACGGATATTAACACATTCACACCGAATGAACTGTTGACAGTTATGCAATTATTTTTCAATTCAGTGGGAATGCCATTCAAGGTTCTGTTCTTCAATTTGTATATTTCTGGATTTTACAAGGCCAAAAAGCTCCTTAGCGAAATGGACAAACGTTGCACCACTTTGAAGGAGCGAGTGGAAGTGCACCAAGGTGTGGTCCGTTGCAACAAGGCCTACCTCATTTACCAGTTCATTTATACCGCGTACACTATTTCAACATTTCTATCGGCGGCTCTTAGTGGAAAATTGCCATGGCGCATCTATAATCCTTTTGTGGATTTTCGAGAAAGTAGATCCAGTTTTTGGAAAGCTGCCCTCAACGAGACAGCACTTATGCTATTTGCTGTGACTCAAACCCTAATGAGTGATATATATCCACTGCTTTATGGTTTGATCCTGAGAGTTCACCTCAAACTTTTGCGACTAAGAGTGGAGAGCCTGTGCACAGATTCTGGAAAAAGCGATGCTGAAAACGAGCAAGATTTGATTAACTATGCTGCAGCAATACGACCAGCGGTTACCCGCACAATTTTCGTTCAATTCCTCTTGATCGGAATTTGCCTTGGCCTTTCAATGATCAATCTACTCTTCTTTGCCGACATCTGGACAGGATTGGCCACAGTGGCTTACATCAATGGTCTAATGGTGCAGACATTTCCATTTTGCTTCGTTTGTGATCTACTCAAAAAGGATTGTGAACTTCTTGTGTCGGCCATATTTCATTCCAACTGGATTAATTCAAGCCGCAGTTACAAGTCATCTTTGAGATATTTTCTGAAGAACGCCCAGAAATCAATTGCTTTTACAGCCGGCTCTATTTTTCCCATTTCTACTGGCTCGAATATTAAGGTGGCTAAGCTGGCATTTTCGGTGGTTACTTTTGTCAATCAACTTAACATAGCTGACAGAT TGACAAAGAAC DOR111(SEQ ID NO: 38) MLFRKRKPKSDDEVITFDELTRFPMTFYKTIGEDLYSDRDPNVIRRYLLRFYLVLGFLNFNAYVVGEIAYFIVHIMSTTTLLEATAVAPCIGFSFMADFKQFGLTVNRKRLVRLLDDLKEIFPLDLEAQRKYNVSFYRKHMNRVMTLFTILCMTYTSSFSFYPAIKSTIKYYLMGSEIFERNYGFHILFPYDAETDLTVYWFSYWGLAHCAYVAGVSYVCVDLLLIATITQLTMHFNFIANDLEAYEGGDHTDEENIKYLHNLVVYHARALDINKKCTFQSSRIGHSAFNQNWLPCSTKYKRILQFIIARSQKPASIRPPTFPPISFNTFMKVISMSYQFFALLRTTYYG DOR111nt (SEQ ID NO:37) ATGCTGTTCCGCAAACGTAAGCCAAAAAGTGACGATGAAGTCATCACCTTCGACGAACTTACCCGGTTTCCGATGACTTTCTACAAGACCATCGGCGAGGATCTGTACTCCGATAGGGATCCGAATGTGATAAGGCGTTACCTGCTACGTTTTTATCTGGTACTCGGTTTTCTCAACTTCAATGCCTATGTGGTGGGCGAAATCGCGTACTTTATAGTCCATATAATGTCGACGACTACTCTTTTGGAGGCCACTGCAGTGGCACCGTGCATTGGCTTCAGCTTCATGGCCGACTTTAAGCAGTTCGGTCTCACAGTGAATAGAAAGCGATTGGTCAGATTGCTGGATGATCTCAAGGAGATATTTCCTTTAGATTTAGAAGCGCACCGGAAGTATAACGTATCGTTTTACCGGAAACACATGAACAGGGTCATGACCCTATTCACCATCCTCTGCATGACCTACACCTCGTCATTTAGCTTTTATCCAGCCATCAAGTCGACCATAAAGTATTACCTTATGGGATCGGAAATCTTTGAGCGCAACTACGGATTTCACATTTTGTTTCCCTACGACGCAGAAACGGATCTGACGGTCTACTGGTTTTCCTACTGGGGATTGGCTCATTGTGCCTATGTGGCCGGAGTTTCCTACGTCTGCGTGGATCTCCTGCTGATCGCGACCATAACCCAGCTGACCATGCACTTCAACTTTATAGCGAATGATTTGGAGGCCTACGAAGGAGGTGATCATACGGATGAAGAAAATATCAAATACCTGCACAACTTGGTCGTCTATCATGCCAGGGCGCTGGATATTAACAAGAAATGTACATTTCAGAGCTCTCGGATTGGCCATTCGGCATTTAATCAGAACTGGTTGCCATGCAGCACCAAATACAAACGCATCCTGCAATTTATTATCGCGCGCAGCCAGAAGCCCGCCTCTATAAGACCGCCTACCTTTCCACCCATATCTTTTAATACCTTTATGAAGGTAATCAGCATGTCGTATCAGTTTTTTGCACTGCTCCGCACCACATATTATGGT DOR114 (SEQ ID NO:40) MLTKKDTQSAKEQEKLKAIPLHSFLKYANVFYLSIGMMAYDHKYSQKWKEVLLHWTFIAQMVNLNTVLISELIYVFLAIGKGSNFLEATMNLSFIGFVIVGDFKIWNISRQRKRLTQVVSRLEELHPQGLAQQEPYNIGHHLSGYSRYSKFYFGMHMVLIWTYNLYWAVYYLVCDFWLGMRQFERMLPYYCWVPWDWSTGYSYYFMYISQNIGGQACLSGQLAADMLMCALVTLVVMHFIRLSAHIESHVAGIGSFQHDLEFLQATVAYHQSLIHLCQDINEIFGVSLLSNFVSSSFIICFVGFQMTIGSKIDNLVMLVLFLFCAMVQVFMIATHAQRLVDASEQIGQAVYNHDWFRADLRYRKMLILIIKRAQQPSRLKATMFLNISLVTVSDLLQLSY KFFALLRTMYVN DOR114nt(SEQ ID NO: 39) ATGTTGACTAAGAAGGATACTCAAAGTGCCAAGGAGCAGGAAAAGTTGAAGGCCATTCCATTGCACAGCTTTCTGAAATATGCCAACGTGTTCTATTTATCGATTGGAATGATGGCCTACGATCACAAGTACAGTCAAAAGTGGAAGGAGGTCCTGCTGCACTGGACATTCATTGCCCAGATGGTCAATCTGAATACAGTGCTCATCTCGGAACTGATTTACGTATTCCTGGCGATCGGCAAAGGTAGCAATTTTCTGGAGGCCACCATGAATCTGTCTTTCATTGGATTTGTCATCGTTGGTGACTTCAAAATCTGGAACATTTCGCGGCAGAGAAAGAGACTCACCCAAGTGGTCAGCCGATTGGAAGAACTGCATCCGCAAGGCTTGGCTCAACAAGAACCCTATAATATAGGGCATCATCTGAGCGGCTATAGCCGATATAGCAAATTTTACTTCGGCATGCACATGGTGCTGATATGGACGTACAACCTGTATTGGGCCGTTTACTATCTGGTCTGTGATTTCTGGCTGGGAATGCGTCAATTTGAGAGGATGCTGCCCTACTACTGCTGGGTTCCCTGGGATTGGAGTACCGGATATAGCTACTATTTCATGTATATCTCACAGAATATCGGCGGTCAGGCTTGTCTGTCCGGTCAGCTAGCAGCTGACATGTTAATGTGCGCCCTGGTCACTTTGGTGGTGATGCACTTCATCCGGCTTTCCGCTCACATCGAGAGTCATGTTGCGGGCATTGGCTCATTCCAGCACCATTTGGAGTTCCTCCAAGCGACGGTGGCGTATCACCAGAGCTTGATCCACCTCTGCCAGGATATCAATGAGATATTCGGTGTTTCACTGTTGTCCAACTTTGTATCCTCGTCGTTTATCATCTGCTTCGTGGGTTTCCAGATGACCATCGGCAGCAAGATCGACAACCTGGTAATGCTTGTGCTTTTCCTGTTTTGTGCCATGGTTCAGGTCTTCATGATTGCCACCCATGCTCAGAGGCTCGTTGATGCGAGTGAACAGATTGGTCAAGCGGTCTATAATCACGACTGGTTCCGTGCTGATCTGCGGTATCGTAAAATGCTGATCCTGATTATTAAGAGGGCCCAACAGCCGAGTCGACTCAAGGCCACAATGTTCCTGAACATCTCACTGGTCACCGTGTCGGATCTCTTGCAACTCTCGTACAAATTCTTTGCCCTTCTGCGCACAATGTACGTGAAT DOR115 (SEQ ID NO: 42)MEKLMKYASFFYTAVGIRPYTNGEESKMNKLIFHIVFWSNVINLSFVGLFESIYVYSAFMDNKFLEAVTALSYIGFVTVGMSKMFFIRWKKTAITELINELKEIYPNGLIREERYNLPMYLGTCSRISLIYSLLYSVLIWTFNLFCVMEYWVYDKWLNIRVVGKQLPYLMYIPWKWQDNWSYYPLLFSQNFAGYTSAAGQISTDVLLCAVATQLVMHFDFLSNSMERHELSGDWKKDSRFLVDIVRYHERILRLSDAVNDIFGIPLLLNFMVSSFVICFVGFQMTVGVPPDIVVKLFLFLVSSMSQVYLICHYGQLVADASYGFSVATYNQKWYKADVRYKRALVIIIARSQKVTFLKATIFLDITRSTMTDVRNCVLSV DOR115nt (SEQ ID NO: 41)ATGGAGAAGCTAATGAAGTACGCTAGCTTCTTCTACACAGCAGTGGGCATACGGCCATATACCAATGGTGAAGAATCCAAAATGAACAAACTTATATTTCACATAGTTTTTTGGTCCAATGTGATTAACCTCAGCTTCGTTGGATTATTTGAGAGCATTTACGTTTACAGTGCCTTCATGGATAATAAGTTCCTGGAAGCAGTCACTGCGTTGTCCTACATTGGCTTCGTAACCGTAGGCATGAGCAAGATGTTCTTCATCCGGTGGAAGAAAACGGCTATAACTGAACTGATTAATGAATTGAAGGAGATCTATCCGAATGGTTTGATCCGAGAGGAAAGATACAATCTGCCGATGTATCTGGGCACCTGCTCCAGAATCAGCCTTATATATTCCTTGCTCTACTCTGTTCTCATCTGGACATTCAACTTGTTTTGTGTAATGGAGTATTGGGTCTATGACAAGTGGCTCAACATTCGAGTGGTGGGCAAACAGTTGCCGTACCTCATGTACATTCCTTGGAAATGGCAGGATAACTGGTCGTACTATCCACTGTTATTCTCCCAGAATTTTGCAGGATACACATCTGCAGCTGGTCAAATTTCAACCGATGTCTTGCTCTGCGCGGTGGCCACTCAGTTGGTAATGCACTTCGACTTTCTCTCAAATAGTATGGAACGCCACGAATTGAGTGGAGATTGGAAGAAGGACTCCCGATTTCTGGTGGACATTGTTAGGTATCACGAACGTATACTCCGCCTTTCAGATGCAGTGAACGATATATTTGGAATTCCACTACTACTCAACTTCATGGTATCCTCGTTCGTCATCTGCTTCGTGGGATTCCAGATGACTGTTGGAGTTCCGCCGGATATAGTTGTGAAGCTCTTCCTCTTCCTTGTCTCTTCGATGAGTCAGGTCTATTTGATTTGTCACTATGGTCAACTGGTGGCCGATGCTAGCTACGGATTTTCGGTTGCCACCTACAATCAGAAGTGGTATAAAGCCGATGTGCGCTATAAACGAGCCTTGGTTATTATTATAGCTAGATCGCAGAAGGTAACTTTTCTAAAGGCCACTATATTCTTGGATATTACCAGGTCCACTATGACAGATGTACGCAACTGTGTATTGTCAGTG DOR116 (SEQ ID NO: 44)MELLPLAMLMYDGTRVTAMQYLIPGLPLENNYCYVVTYMIQTVTMLVQGVGFYSGDLFVFLGLTQILTFADMLQVKVKELNDALEQKAEYRALVRVGASIDGAENRQRLLLDVIRWHQLFTDYCRAINALYYELIATQVLSMALAMMLSFCINLSSFHMPSAIFFVVSAYSMSIYCILGTILEFAYDQVYESICNVTWYELSGEQRKLFGFLLRESQYPHNIQILGVMSLSVRTALQIVKLIYSVSMMMM NRA DOR116nt (SEQ IDNO: 43) ATGGAACTCCTGCCATTGCCCATGCTAATGTACGATGGAACCCGGGTTACTGCGATGCAGTATTTAATTCCGGGTCTACCGCTTGAGAACAATTATTGCTACGTAGTCACGTACATGATTCAGACGGTGACAATGCTCGTGCAAGGAGTCGGATTCTACTCCGGTGATTTGTTCGTATTTCTCGGCTTAACGCAGATCCTAACTTTCGCCGATATGCTGCAGGTGAAGGTGAAAGAGCTAAACGATGCCCTGGAACAAAAAGCGGAATACAGAGCTCTAGTCCGAGTTGGAGCTTCTATTGATGGAGCGGAAAATCGTCAACGCCTTCTCTTGGATGTTATAAGATGGCATCAATTATTCACGGACTACTGTCGCGCCATAAATGCCCTCTACTACGAATTGATCGCCACTCAGGTTCTTTCGATGGCTTTGGCCATGATGCTCAGCTTCTGCATTAATTTGAGCAGCTTTCACATGCCTTCGGCTATCTTTTTCGTGGTTTCTGCCTACAGCATGTCCATCTATTGCATTCTGGGCACCATTCTTGAGTTTGCATATGACCAGGTGTACGAGAGCATCTGTAATGTGACCTGGTATGAGTTGAGTGGCGAACAGCGAAAGCTTTTTGGTTTTTTGTTGCGGGAATCCCAGTATCCGCACAATATTCAGATACTTGGAGTTATGTCGCTTTCCGTGAGAACGGCTCTGCAGATTGTTAAACTAATTTATAGCGTATCCATGATGATGATG AATCGGGCG DOR117 (SEQID NO: 46) MDLRRWFPTLYTQSKDSPVRSRDATLYLLRCVFLMGVRKPPAKFFVAYVLWSFALNFCSTFYQPIGFLTGYISHLSEFSPGEFLTSLQVAFNAWSCSTKVLIVWALVKRFDEANNLLDEMDRRITDPGERLQIHRAVSLSNRIFFFFMAVYMVYATNTFLSAIFIGRPPYQNYYPFLDWRSSTLHLALQAGLEYFAMAGACFQDVCVDCYPVNFVLVLRAHMSIFAERLRRLGTYPYESQEQKYERLVQCIQDHKVILRFVDCLRPVISGTIFVQFLVVGLVLGFTLINIVLFANLGSAIAALSFMAAVLLETTPFCILCNYLTEDCYKLADALFQSNWIDEEKRYQKTLMYFLQKLQQPITFMAMNVFPISVGTNISVSRCAL DOR117nt (SEQ ID NO: 45)ATGGATCTGCGAAGGTGGTTTCCGACCTTGTACACCCAGTCGAAGGATTCGCCAGTTCGCTCCCGAGACGCGACCCTGTACCTCCTACGCTGCGTCTTCTTAATGGGCGTCCGCAAGCCACCTGCCAAGTTTTTCGTGGCCTACGTGCTCTGGTCCTTCGCACTGAATTTCTGCTCAACATTTTATCAGCCAATTGGCTTTCTCACAGGCTATATAAGCCATTTATCAGAGTTCTCCCCGGGAGAGTTTCTAACTTCGCTGCAGGTGGCCTTTAATGCTTGGTCCTGCTCTACAAAAGTCCTGATAGTGTGGGCACTAGTTAAGCGCTTTGACGAGGCTAATAACCTTCTCGACGAGATGGATAGGCGTATCACAGACCCCGGAGAGCGTCTTCAGATTCATCGCGCTGTCTCCCTCAGTAACCGTATATTCTTCTTTTTCATGGCAGTCTACATGGTTTATGCCACTAATACGTTTCTGTCGGCGATCTTCATTGGAAGGCCACCGTACCAAAATTACTACCCTTTTCTGGACTGGCGATCTAGCACTCTGCATCTAGCTCTGCAGGCCGGTCTGGAATACTTCGCCATGGCTGGCGCCTGCTTCCAGGACGTTTGCGTTGATTGCTACCCAGTCAATTTCGTTTTGGTCCTGCGTGCCCACATGTCGATCTTCGCGGAGCGCCTTCGACGTTTGGGAACTTATCCTTATGAAAGCCAGGAGCAGAAATATGAACGATTGGTTCAGTGCATACAAGATCACAAAGTAATTTTGCGATTTGTTGACTGCCTGCGTCCTGTTATTTCTGGTACCATCTTCGTGCAATTCTTGGTTGTGGGGTTGGTGCTGGGCTTTACCCTAATTAACATTGTCCTGTTCGCCAACTTGGGATCGGCCATCGCAGCGCTCTCGTTTATGGCCGCAGTGCTTCTAGAGACGACTCCCTTCTGCATATTGTGCAATTATCTCACAGAAGACTGCTACAAGCTGGCCGATGCCCTGTTTCAGTCAAACTGGATTGATGAGGAGAAACGATACCAAAAGACACTCATGTACTTCCTACAGAAACTGCAGCAGCCTATAACCTTCATGGCTATGAACGTGTTTCCAATATCTGTGGGAACTAACATCAGTGTAAGCAGATGTGCCC TT DOR118 (SEQ ID NO:48) MKFIGWLPPKQGVLRYVYLTWTLMTFVWCTTYLPLGFLGSYMTQIKSFSPGEFLTSLQVCINAYGSSVKVAITYSMLWRLIKAKNILDQLDLRCTAMEEREKIHLVVARSNHAFLIFTFVYCGYAGSTYLSSVLSGRPPWQLYNPFIDWHDGTLKLWVASTLEYMVMSGAVLQDQLSDSYPLIYTLILPAHLDMLRERIRRLRSDENLSEAESYEELVKCVMDHKLILRYCAIIKPVIQGTIFTQFLLIGLVLGFTLINVFFFSDIWTGIASFMFVITILLQTFPFCYTCNLIMEDCESLTHAIFQSNWVDASRRYKTTLLYFLQNVQQPIVFIAGGIFQISMSSNISVAKFAFSVITITKQMNIADKFKTD DOR118nt (SEQ ID NO: 47)ATGAAGTTTATTGGATGGCTGCCCCCCAAGCAGGGTGTGCTCCGGTATGTGTACCTCACCTGGACGCTAATGACGTTCGTGTGGTGTACAACGTACCTGCCGCTTGGCTTCCTTGGTAGCTACATGACGCAGATCAAGTCCTTCTCCCCTGGAGAGTTTCTCACTTCACTCCAGGTGTGCATTAATGCCTACGGCTCATCGGTAAAAGTTGCAATCACATACTCCATGCTCTGGCGCCTTATCAAGGCCAAGAACATTTTGGACCAGCTGGACCTGCGCTGCACCGCCATGGAGGAGCGCGAAAAGATCCACCTAGTGGTGGCCCGCAGCAACCATGCCTTTCTCATCTTCACCTTTGTCTACTGCGGATATGCCGGCTCCACCTACCTGAGCTCGGTTCTCAGCGGGCGTCCGCCCTGGCAGCTGTACAATCCCTTTATTGATTGGCATGACGGCACACTCAAGCTCTGGGTGGCCTCCACGTTGGAGTACATGGTGATGTCAGGCGCCGTTCTGCAGGATCAACTCTCGGACTCTTACCCATTGATCTATACCCTCATCCTTCGTGCTCACTTGGACATGCTAAGGGAGCGCATCCGACGCCTCCGTTCCGATGAGAACCTGAGCGAGGCCGAGAGCTATGAAGAGCTGGTCAAATGTGTGATGGACCACAAGCTCATTCTAAGATACTGCGCGATTATTAAACCAGTAATCCAGGGGACCATCTTCACACAGTTTCTGCTGATCGGCCTGGTTCTGGGCTTCACGCTGATCAACGTGTTTTTCTTCTCAGACATCTGGACGGGCATCGCATCATTTATGTTTGTTATAACCATTTTGCTGCAGACCTTCCCCTTCTGCTACACATGCAACCTCATCATGGAGGACTGCGAGTCCTTGACCCATGCTATTTTCCAGTCCAACTGGGTGGATGCCAGTCGTCGCTACAAAACAACACTACTGTATTTTCTCCAAAACGTGCAGCAGCCTATCGTTTTCATTGCAGGCGGTATCTTTCAGATATCCATGAGCAGCAACATAAGTGTGGCAAAGTTTGCTTTCTCCGTGATAACCATTACCAAGCAAATGAATATAGCTGA CAAATTTAAGACGGACDOR119 (SEQ ID NO: 50)MAVFKLIKPAPLTEKVQSRQGNIYLYRAMWLIGWIPPKEGVLRYVYLFWTCVPFAFGVFYLPVGFIISYVQEFKNFTPGEFLTSLQVCINVYGASVKSTITYLFLWRLRKTEILLDSLDKRLANDSDRERIHNMVARCNYAFLIYSFIYCGYAGSTFLSYALSGRPPWSVYNPFIDWRDGMGSLWIQAIFEYITMSFAVLQDQLSDTYPLMFTIMFRAHMEVLKDHVRSLRMDPERSEADNYQDLVNCVLDHKTILKCCDMIRPMISRTIFVQFALIGSVLGLTLVNVFFFSNFWKGVASLLFVITILLQTFPFCYTCNMLIDDAQDLSNEIFQSNWVDAEPRYKATLVLFMHHVQQPIIFIAGGIFPISMNSNITVAKFAFSIITIVRQMNLAEQFQ DOR119nt (SEQ ID NO:49) ATGGCGGTGTTCAAGCTAATCAAACCGGCTCCGTTGACCGAGAAGGTGCAGTCCCGCCAGGGGAATATATATCTGTACCGTGCCATGTGGCTCATCGGATGGATTCCGCCGAAGGAGGGAGTCCTGCGCTACGTGTATCTCTTCTGGACCTGCGTGCCCTTCGCCTTCGGGGTGTTTTACCTGCCCGTGGGCTTCATCATCAGCTACGTGCAGGAGTTCAAGAACTTCACGCCGGGCGAGTTCCTTACCTCGCTGCAGGTGTGCATCAATGTGTATGGCGCCTCGGTGAAGTCCACCATCACCTACCTCTTCCTCTGGCGACTGCGCAAGACGGAGATCCTTCTGGACTCCCTGGACAAGAGGCTGGCGAACGACAGCGATCGCGAGAGGATCCACAATATGGTGGCGCGCTGCAACTACGCCTTTCTCATCTACAGCTTCATCTACTGCGGATACGCGGGTTCCACTTTCCTGTCCTACGCCCTCAGTGGTCGTCCTCCGTGGTCCGTCTACAATCCCTTCATCGATTGGCGCGATGGCATGGGCAGCCTGTGGATCCAGGCCATATTCGAGTACATCACCATGTCCTTCGCCGTGCTGCAGGACCAGCTATCCGACACGTATCCCCTGATGTTCACCATTATGTTCCGGGCCCACATGGAGGTCCTCAAGGATCACGTGCGGAGCCTGCGCATGGATCCCGAGCGCAGTGAGGCAGACAACTATCAGGATCTGGTGAACTGCGTGCTGGACCACAAGACTATACTGAAATGCTGTGACATGATTCGCCCCATGATATCCCGCACCATCTTCGTGCAATTCGCGCTGATTGGTTCCGTTTTGGGCCTGACCCTGGTGAACGTGTTCTTCTTCTCGAACTTCTGGAAGGGCGTGGCCTCGCTCCTGTTCGTCATCACCATCCTGCTGCAGACCTTCCCGTTCTGCTACACCTGCAACATGCTGATCGACGATGCCCAGGATCTGTCCAACGAGATTTTCCAGTCCAACTGGGTGGACGCGGAGCCGCGCTACAAGGCGACGCTGGTGCTCTTCATGCACCATGTTCAGCAGCCCATAATCTTCATTGCCGGAGGCATCTTTCCCATCTCTATGAACAGCAACATAACCGTGGCCAAGTTCGCCTTCAGCATCATTACAATAGTGCGACAAATGAATCTGGCCGAGCAGTTCCAG DOR120 (SEQ ID NO: 52)MTKFFFKRLQTAPLDQEVSSLDASDYYYRIAFFLGWTPPKGALLRWIYSLWTLTTMWLGIVYLPLGLSLTYVKHFDRFTPTEFLTSLQVDINCIGNVIKSCVTYSQMWRFRRMNELISSLDKRCVTTTQRRIFHKMVARVNLIVILFLSTYLGFCFLTLFTSVFAGKAPWQLYNPLVDWRKGHWQLWIASILEYCVVSIGTMQELMSDTYAIVFISLFRCHLAILRDRIANLRQDPKLSEMEHYEQMVACIQDHRTIIQCSQIIRPILSITIFAQFMLVGIDLGLAAISILFFPNTIWTIMANVSFIVAICTESFPCCMLCEHLIEDSVHVSNALFHSNWITADRSYKSAVLYFLHRAQQPIQFTAGSTFPISVQSNIAVAKFAFTIITIVNQMNLGEKF FSDRSNGDINP DOR120nt(SEQ ID NO: 51) ATGACCAAGTTCTTCTTCAAGCGCCTGCAAACTGCTCCACTTGATCAGGAGGTGAGTTCCCTTGATGCCAGCGACTACTACTACCGCATCGCATTTTTCCTGGGCTGGACCCCGCCCAAGGGGGCTCTGCTCCGATGGATCTACTCCCTGTGGACTCTGACCACGATGTGGCTGGGTATCGTGTACCTGCCGCTCGGACTCAGCCTCACCTATGTGAAGCACTTCGATAGATTCACGCCGACGGAGTTCCTGACCTCCCTGCAGGTGGATATCAACTGCATCGGGAACGTGATCAAGTCATGCGTAACTTATTCCCAGATGTGGCGTTTTCGCCGGATGAATGAGCTTATCTCGTCCCTGGACAAGAGATGTGTGACTACGACACAGCGTCGAATTTTCCATAAGATGGTGGCACGGGTTAATCTCATCGTGATTCTGTTCTTGTCCACGTACTTGGGCTTCTGCTTTCTAACTCTGTTCACTTCGGTTTTCGCTGGCAAAGCTCCTTGGCAGCTGTACAACCCACTGGTGGACTGGCGGAAAGGCCATTGGCAGCTATGGATTGCCTCCATCCTGGAGTACTGTGTGGTCTCCATTGGCACCATGCAGGAGTTGATGTCCGACACCTACGCCATAGTGTTCATCTCCTTGTTCCGCTGCCACCTGGCTATTCTCAGAGATCCCATAGCTAATCTGCGGCAGGATCCGAAACTCAGTGAGATGGAACACTATGAGCAGATGGTGGCCTGCATTCAGGATCATCGAACCATCATACAGTGCTCCCAGATTATTCGACCCATCCTGTCGATCACTATCTTTGCCCAGTTCATGCTGGTTGGCATTGACTTGGGTCTGGCGGCCATCAGCATCCTCTTCTTTCCGAACACCATTTGGACGATCATGGCAAACGTGTCGTTCATCGTGGCCATCTGTACAGAGTCCTTTCCATGCTGCATGCTCTGCGAGCATCTGATCGAGGACTCCGTCCATGTGACCAACGCCCTGTTCCACTCAAACTGGATAACCGCGGACAGGAGCTACAAGTCGGCGGTTCTGTATTTCCTGCACCGGGCTCAGCAACCCATTCAATTCACGGCCGGCTCCATATTTCCCATTTCGGTGCAGAGCAACATAGCCGTGGCCAAGTTCGCGTTCACAATCATCACAATCGTGAACCAAATGAATCTGGGCGAGAAGTTCTTCAGTGACAGGAGCAATGGCGATATAAATCCT DOR121 (SEQ ID NO: 54)MLTDKFLRLQSALFRLLGLELLHEQDVGHRYPWRSICCILSVASFMPLTIAFGLQNVQNVEQLTDSLCSVLVDLLALCKIGLFLWLYKDFKFLIGQFYCVLQTETHTAVAEMIVTRESRRDQFISAMYAYCFITAGLSACLMSPLSMLISYHEQVNCSRNFHFPVCKKKYCLISRILRYSFCRYPWDNMKLSNYIISYFWNVCAALGVALPTVCVDTLFCSLSHNLCALFQIARHKMMHFEGRNTKETHENLKHVFQLYALCLNLGHFLNEYFRPLICQFVAASLHLCVLCYQLSANILQPALLFYAAFTAAVVGQVSIYCFCGSSIHSECQLFGQAIYESSWPHLLQENLQLVSSLKIAMMRSSLGCPIDGYFFEANRETLITVSKAFIKVSKKTPQVN D DOR121 (SEQ ID NO:53) ATGCTGACGGACAAGTTCCTCCGACTGCAGTCCGCTTTATTTCGCCTTCTCGGACTCGAATTGTTGCACGAGCAGGATGTTGGCCATCGATATCCTTGGCGCAGCATCTGCTGCATTCTCTCGGTGGCCAGTTTCATGCCCCTGACCATTGCGTTTGGCCTGCAAAACGTCCAAAATGTGGAGCAATTAACCGACTCACTCTGCTCGGTTCTCGTGGATTTGCTGGCCCTGTGCAAAATCGGGCTTTTCCTTTGGCTTTACAAGGACTTCAAGTTCCTAATAGGGCAGTTCTATTGTGTTTTGCAAACGGAAACCCACACCGCTGTCGCTGAAATGATAGTGACCAGGGAAAGTCGTCGGGATCAGTTCATCAGTGCTATGTATGCCTACTGTTTCATTACGGCTGGCCTTTCGGCCTGCCTGATGTCCCCTCTATCCATGCTGATTAGCTACCACGAACAGGTGAATTGCAGCCGAAATTTCCATTTCCCAGTGTGTAAGAAAAAGTACTGCTTAATATCCAGAATATTAAGATACAGTTTCTGCAGATATCCCTGGGACAATATGAAGCTGTCCAACTACATCATTTCCTATTTCTGGAATGTGTGTGCTGCATTGGGCGTGGCACTGCCCACCGTTTGTGTGGACACACTGTTCTGTTCTCTGAGCCATAATCTCTGTGCCCTATTCCAGATTGCCAGGCACAAAATGATGCACTTTGAGGGCAGAAATACCAAAGAGACTCATGAGAACTTAAAGCACGTGTTTCAACTATATGCGTTGTGTTTGAACCTGGGCCATTTCTTAAACGAATATTTCAGACCGCTCATCTGCCAGTTTGTGGCAGCCTCACTGCACTTGTGTGTCCTGTGCTACCAACTGTCTGCCAATATCCTGCAGCCAGCGTTACTCTTCTATGCCGCATTTACGGCAGCAGTTGTTGGCCAGGTGTCTATATACTGCTTCTGCGGATCGAGCATCCATTCGGAGTGTCAGCTATTTGGCCAGGCCATCTACGAGTCCAGCTGGCCCCATCTGCTGCAGGAAAACCTGCAGCTTGTAAGCTCCTTAAAAATTGCCATGATGCGATCGAGTTTGGGATGTCCCATCGATGGTTACTTCTTCGAGGCCAATCGGGAGACGCTCATCACGGTGAGTAAAGCGTTTATAAAAGTGTCCAAAAAGACACCTCAAGTGAAT GAT DOR14 (SEQ ID NO:56) MDYDRIRPVRFLTGVLKWWRLWPRKESVSTPDWTNWQAYALHVPFTFLFVLLLWLEAIKSRDIQHTADVLLICLTTTALGGKVINIWKYAHVAQGILSEWSTWDLFELRSKQEVDMWRFEHRRFNRVFMFYCLCSAGVIPFIVIQPLFDIPNRLPFWMWTPFDWQQPVLFWYAFIYQATTIPIACACNVTMDAVNWYLMLHLSLCLRMLGQRLSKLQHDDKDLREKFLELIHLHQRLKQQALSIEIFISKSTFTQILVSSLIICFTIYSMQMDLPGFAAMMQYLVAMIMQVMLPTIYGNAVIDSANMLTDSMYNSDWPDMNCRMRRLVLMFMVYLNRPVTLKAGGFFHIGLPLFTKVVFSTLENPCISYLYFRP DOR14nt (SEQ ID NO: 55)ATGGACTACGATCGAATTCGACCGGTGCGATTTTTGACGGGAGTGCTGAAATGGTGGCGTCTCTGGCCGAGGAAGGAATCGGTGTCCACACCGGACTGGACTAACTGGCAGGCATATGCCTTGCACGTTCCATTTACATTCTTGTTTGTGTTGCTTTTGTGGTTGGAGGCAATCAAGAGCAGGGATATACAGCATACCGCCGATGTCCTTTTGATTTGCCTAACCACCACTGCCTTGGGAGGTAAAGTTATCAATATCTGGAAGTATGCCCATGTGGCCCAAGGCATTTTGTCCGAGTGGAGCACGTGGGATCTTTTCGAGCTGAGGAGCAAACAGGAAGTGGATATGTGGCGATTCGAGCATCGACGTTTCAATCGTGTTTTTATGTTTTACTGTTTGTGCAGTGCTGGTGTAATCCCATTTATTGTGATTCAACCGTTGTTTGATATCCCAAATCGATTGCCCTTCTGGATGTGGACACCATTCGATTGGCAGCAGCCTGTTCTCTTCTGGTATGCATTCATCTATCAGGCCACAACCATTCCTATTGCCTGTGCTTGCAACGTAACCATGGACGCTGTTAATTGGTACTTGATGCTGCATCTGTCCTTGTGTTTGCGTATGTTGGGCCAGCGATTGAGTAAGCTTCAGCATGATGACAAGGATCTGAGGGAGAAGTTCCTGGAACTGATCCATCTGCACCAGCGACTCAAGCAACAGGCCTTGAGCATTGAAATCTTTATTTCGAAGAGCACGTTCACCCAAATTCTGGTCAGTTCCCTTATCATTTGCTTCACCATTTACAGCATGCAGATGGACTTGCCAGGATTTGCCGCCATGATGCAGTACCTAGTGGCCATGATCATGCAGGTCATGCTGCCCACCATATATGGTAACGCCGTCATCGATTCTGCAAATATGTTGACCGATTCCATGTACAATTCGGATTGGCCGGATATGAATTGCCGAATGCGTCGCCTAGTTTTAATGTTTATGGTGTACTTAAATCGACCGGTGACCTTAAAAGCCGGTGGCTTTTTTCATATTGGTTTACCTCTGTTTACCAAGGTTGTATTTTCTACTCTGGAAAATCCTTGTATAAGTTATCTTTATTTCAGACCA DOR16 (SEQ ID NO: 58)MTDSGQPAIADHFYRIPRISGLIVGLWPQRIRGGGGRPWHAHLLFVFAFAMVVVGAVGEVSYGCVHLDNLVVALEAFCPGTTKAVCVLKLWVFFRSNRRWAELVQRLRAILWESRRQEAQRMLVGLATTANRLSLLLLSSGTATNAAFTLQPLIMGLYRWIVQLPGQTELPFNIILPSFAVQPGVFPLTYVLLTASGACTVFAFSFVDGFFICSCLYICGAFRLVQQDIRRIFADLHGDSVDVFTEEMNAEVRHRLAQVVERHNAIIDFCTDLTRQFTVIVLMHFLSAAFVLCSTILDIMLVSPFSEAFLWGGYPWVCRATGFSHRLHSAAVLKVFPCFHCLLFFPGFSSRSVLIRFSRFVCLLCGCGCGSLRWQFISA DOR16nt (SEQ ID NO: 57)ATGACTGACAGCGGGCAGCCTGCCATTGCCGACCACTTTTATCGGATTCCCCGCATCTCCGGCCTCATTGTCGGCCTCTGGCCGCAAAGGATAAGGGGCGGGGGCGGTCGTCCTTGGCACGCCCATCTGCTCTTCGTGTTCGCCTTCGCCATGGTGGTGGTGGGTGCGGTGGGCGAGGTGTCGTACGGCTGTGTCCACCTGGACAACCTGGTGGTGGCGCTGGAGGCCTTCTGCCCCGGAACCACCAAGGCGGTCTGCGTTTTGAAGCTGTGGGTCTTCTTCCGCTCCAATCGCCGGTGGGCGGAGTTGGTCCAGCGCCTGCGGGCTATTTTGTGGGAATCGCGGCGGCAGGAGGCCCAGAGGATGCTGGTCGGACTGGCCACCACGGCCAACAGGCTCAGCCTGTTGTTGCTCAGCTCTGGCACGGCGACAAATGCCGCCTTCACCTTGCAACCGCTGATTATGGGTCTCTACCGCTGGATTGTGCAGCTGCCAGGTCAAACCGAGCTGCCCTTTAATATCATACTGCCCTCGTTTGCCGTGCAGCCAGGAGTCTTTCCGCTCACCTACGTGCTGCTGACCGCTTCCGGTGCCTGCACCGTTTTCGCCTTCAGCTTCGTGGACGGATTCTTCATTTGCTCGTGCCTCTACATCTGCGGCGCTTTCCGGCTGGTGCAGCAGGACATTCGCAGGATATTTGCCGATTTGCATGGCGACTCAGTGGATGTGTTCACCGAGGAGATGAACGCGGAGGTGCGGCACAGACTGGCCCAAGTTGTCGAGCGGCACAATGCGATTATCGATTTCTGCACGGACCTAACACGCCAGTTCACCGTTATCGTTTTAATGCATTTCCTGTCCGCCGCCTTCGTCCTCTGCTCGACCATCCTGGACATCATGTTGGTGAGCCCCTTTTCAGAGGCCTTCCTTTGGGGCGGGTATCCTTGGGTTTGTCGCGCCACTGGCTTTTCGCATCGCCTGCATTCGGCGGCTGTTTTAAAAGTTTTTCCCTGTTTTCACTGTTTGCTGTTTTTCCCTGGCTTTTCCAGCCGCTCCGTTCTGATTCGGTTTTCCCGATTTGTTTGTTTGCTTTGTGGCTGCGGCTGCGGCTCTCTCCGGTGGCAATTTATAAGCGCATGA DOR19g (SEQ ID NO: 22)MVTEDFYKYQVWYFQILGVWQLPTWAADHQRRFQSMRFGFILVILFIMLLLFSFEMLNNISQVREILKVFFMFATEISCMAKLLHLKLKSRKLAGLVDAMLSPEFGVKSEQEMQMLELDRVAVVRMRNSYGIMSLGAASLILIVPCFDNFGELPLAMLEVCSIEGWICYWSQYLFHSICLLPTCVLNITYDSVAYSLLCFLKVQLQMLVLRLEKLGPVIEPQDNEKIAMELRECAAYYNRIVRFKDLVELFIKGPGSVQLMCSVLVLVSNLYDMSTMSIANGDAIFMLKTCIYQLVMLWQIFIICYASNEVTVQSSRLCHSIYSSQWTGWNRANRRIVLLMMQRFNSPMLLSTFNPTFAFSLEAFGSVGQQKFLYISFITGYALLLSDRQLLLQLLRTAEARQQLNFETPQHLKIFKPIFKSTQNVMHVH DOR19gnt (SEQ ID NO: 21)ATGGTTACGGAGGACTTTTATAAGTACCAGGTGTGGTACTTCCAAATCCTTGGTGTTTGGCAGCTCCCCACTTGGGCCGCAGACCACCAGCGTCGTTTTCAGTCCATGAGGTTTGGCTTCATCCTGGTCATCCTGTTCATCATGCTGCTGCTTTTCTCCTTCGAAATGTTGAACAACATTTCCCAAGTTAGGGAGATCCTAAAGGTATTCTTCATGTTCGCCACGGAAATATCCTGCATGGCCAAATTATTGCATTTGAAGTTGAAGAGCCGCAAACTCGCTGGCTTGGTTGATGCGATGTTGTCCCCAGAGTTCGGCGTTAAAAGTGAACAGGAAATGCAGATGCTGGAATTGGATAGAGTGGCGGTTGTCCGCATGAGGAACTCCTACGGCATCATGTCCCTGGGCGCGGCTTCCCTGATCCTTATAGTTCCCTGTTTCGACAACTTTGGCGAGCTACCACTGGCCATGTTGGAGGTATGCAGCATCGAGGGATGGATCTGCTATTGGTCGCAGTACCTTTTCCACTCGATTTGCCTGCTGCCCACTTGTGTGCTGAATATAACCTACGACTCGGTGCCCTACTCGTTGCTCTGTTTCTTGAAGGTTCAGCTACAAATGCTGGTCCTGCGATTAGAAAAGTTGGGTCCTGTGATCGAACCCCAGGATAATGAGAAAATCGCAATGGAACTGCGTGAGTGTGCCGCCTACTACAACAGGATTGTTCGTTTCAAGGACCTGGTGGAGCTGTTCATAAAGGGGCCAGGATCTGTGCAGCTCATGTGTTCTGTTCTGGTGCTGGTGTCCAACCTGTACGACATGTCCACCATGTCCATTGCAAACGGCGATGCCATCTTTATGCTCAAGACCTGTATCTATCAGCTGGTGATGCTCTGGCAGATCTTCATCATTTGCTACGCCTCCAACGAGGTAACTGTCCAGAGCTCTAGGTTGTGTCACAGCATCTACAGCTCCCAATGGACGGGATGGAACAGGGCAAACCGCCGGATTGTCCTTCTCATGATGCAGCGCTTTAATTCCCCGATGCTCCTGAGCACCTTTAACCCCACCTTTGCTTTCAGCTTGGAGGCCTTTGGTTCTGTAGGGCAGCAGAAATTCCTTTATATATCATTTATTACTGGTTATGCTCTTCTCCTTTCAGATCGTCAACTGCTCCTACAGCTACTTCGCACTGCTGAAGCGCGTCAACAGTTAAATTTCGAAACACCGCAGCACCTAAAGATTTTCAAGCCGATTTTTAAAAGCACTCAAAACGTTATGCACGTACAT DOR20 (SEQ ID NO: 60)MSKGVEIFYKGQKAFLNILSLWPQIERRWRIIHQVNYVHVIVFWVLLFDLLLVLHVMANLSYMSEVVKAIFILATSAGHTTKLLSIKANNVQMEELFRRLDNEEFRPRGANEELIFAAACERSRKLRDFYGALSFAALSMILIPQFALDWSHLPLKTYNPLGENTGSPAYWLLYCYQCLALSVSCITNIGFDSLCSSLFIFLKCQLDILAVRLDKIGRLITTSGGTVEQQLKENIRYHMTIVELSKTVERLLCKPISVQIFCSVLVLTANFYAIAVVSCEFATRRLSVCDLSGVHVDSDFYIVLLCRVGIPYPKCLPRPVMNFIVSEVTQRSLDLPHELYKTSWVDWDYRSRRIALLFMQRLHSTLRIRTLNPSLGFDLMLFSSVSSFRVLTFLCTVANF HNEAH DOR20nt (SEQ IDNO: 59) ATGAGCAAAGGAGTAGAAATCTTTTACAAGGGCCAGAAGGCATTCTTGAACATCCTCTCGTTGTGGCCTCAGATAGAACGCCGGTGGAGAATCATCCACCAGGTGAACTATGTCCACGTAATTGTGTTTTGGGTGCTGCTCTTTGATCTCCTCTTGGTGCTCCATGTGATGGCTAATTTGAGCTACATGTCCGAGGTTCTGAAAGCCATCTTTATCCTGGCCACCAGTGCAGGGCACACCACCAAGCTGCTGTCCATAAAGGCGAACAATGTGCAGATGGAGGAGCTCTTTAGGAGATTGGATAACGAAGAGTTCCGTCCTAGAGGCGCCAACGAAGAGTTGATCTTTGCAGCAGCCTGTGAAAGAAGTAGGAAGCTTCGGGACTTCTATGGAGCGCTTTCGTTTGCCGCCTTGAGCATGATTCTCATACCCCAGTTCGCCTTGGACTGGTCCCACCTTCCGCTCAAAACATACAATCCGCTTGGCGAGAATACCGGCTCACCTGCTTATTGGCTCCTCTACTGCTATCAGTGTCTGGCCTTGTCCGTATCCTGCATCACCAACATAGGATTCGACTCACTCTGCTCCTCACTGTTCATCTTCCTCAAGTGCCAGCTGGACATTCTGGCCGTGCGACTGGACAAGATCGGTCGGTTAATCACTACTTCTGGTGGCACTGTGGAACAGCAACTTAAGGAAAATATCCGCTATCACATGACCATCGTTGAACTGTCGAAAACCGTGGAGCGTCTACTTTGCAAGCCGATTTCGGTGCAGATCTTCTGCTCGGTTTTGGTGCTGACTGCCAATTTCTATGCCATTGCTGTGGTGAGCTGTGAATTCGCAACAAGAAGACTATCAGTATGTGACCTATCAGGCGTGCATGTTGATTCAGATTTTTATATTGTGCTACTATGCCGGGTGGGTATTCCATATCCGAAATGCCTCCCCAGGCCAGTAATGAATTTCATCGTCAGTGAGGTAACCCAGCGCAGCCTGGACCTTCCGCACGAGCTGTACAAGACCTCCTGGGTGGACTGGGACTACAGGAGCCGAAGGATTGCGCTCCTCTTTATGCAACGCCTTCACTCGACCTTGAGGATTAGGACACTTAATCCAAGTCTTGGTTTTGACTTAATGCTCTTCAGCTCGGTGAGTTCTTTCCGTGTTTTGACTTTTTTGTGCACTGTAGCCAATTTC CATAATGAGGCTCAT DOR24(SEQ ID NO: 24) MDSFLQVQKSTIALLGFDLFSENREMWKRPYRAMNVFSIAAIFPFILAAVLHNWKNVLLLADAMVALLITILGLFKFSMILYLRRDFKRLIDKFRLLMSNEAEQGEEYAEILNAANKQDQRMCTLFRTCFLLAWALNSVLPLVRMGLSYWLAGHAEPELPFPCLFPWNIHIIRNYVLSFIWSAFASTGVVLPAVSLDTIFCSFTSNLCAFFKIAQYKVVRFKGGSLKESQATLNKVFALYQTSLDMCNDLNQCYQPIICAQFFISSLQLCMLGYLFSITFAQTEGVYYASFIATIIIQAYIYCYCGENLKTESASFEWAIYDSPWHESLGAGGASTSICRSLLISMMRAHRGFRITGYFFEANMEAFSSIVRTAMSYITMLRSFS DOR24nt (SEQ ID NO: 23)GGCACGAGCCTTGTCGACATGGACAGTTTTCTGCAAGTACAGAAGAGCACCATTGCTCTTCTGGGCTTTGATCTCTTTAGTGAAAATCGAGAAATGTGGAAACGCCCCTATAGAGCAATGAATGTGTTTAGCATAGCTGCCATTTTTCCCTTTATCCTGGCAGCTGTGCTCCATAATTGGAAGAATGTATTGCTGCTGGCCGATGCCATGGTGGCCCTACTAATAACCATTCTGGGCCTATTCAAGTTTAGCATGATACTTTACTTACGTCGCGATTTCAAGCGACTGATTGACAAATTTCGTTTGCTCATGTCGAATGAGGCGGAACAGGGCGAGGAATACGCCGAGATTCTCAACGCAGCAAACAAGCAGGATCAACGAATGTGCACTCTGTTTAGGACTTGTTTCCTCCTCGCCTGGGCCTTGAATAGTGTTCTGCCCCTCGTGAGAATGGGTCTCAGCTATTGGTTAGCAGGTCATGCAGAGCCCGAGTTGCCTTTTCCCTGTCTTTTTCCCTGGAATATCCACATCATTCGCAATTATGTTTTGAGCTTCATCTGGAGCGCTTTCGCCTCGACAGGTGTGGTTTTACCTGCTGTCAGCTTGGATACCATATTCTGTTCCTTCACCAGCAACCTGTGCGCCTTCTTCAAAATTGCGCAGTACAAGGTGGTTAGATTTAAGGGCGGATCCCTTAAAGAATCACAGGCCACATTGAACAAAGTCTTTGCCCTGTACCAGACCAGCTTGGATATGTGCAACGATCTGAATCAGTGCTACCAACCGATTATCTGCGCCCAGTTCTTCATTTCATCTCTGCAACTCTGCATGCTGGGATATCTGTTCTCCATTACTTTTGCCCAGACAGAGGGCGTGTACTATGCCTCTTTCATAGCCACCATCATTATACAAGCCTATATCTACTGCTACTGCGGGGAGAACCTGAAGACGGAGAGTGCCAGCTTCGAGTGGGCCATCTACGACAGTCCGTGGCACGAGAGTTTGGGTGCTGGTGGAGCCTCTACCTCGATCTGCCGATCCTTGCTGATCAGCATGATGCGGGCTCATCGGGGATTCCGCATTACGGGATACTTCTTCGAGGCAAACATGGAGGCCTTCTCATCGATTGTTCGCACGGCTATGTCCTACATCACAATGCTGAGATCATTCTCCTAAATGTGGTTTGACCACAAGGCTTTGGATTGATTTTTGTGCAATTTTTGTTTTATTGCTGAGCATGCGTTGCCGTACGACATTTAACAATCGATCTTACGTAATTTACATATGATAATCTCACATATTGTTCGTTAAGCACTAAGTAGAATGTAGAATGTGAATTGGCTGTAGAAATGCACAGATGAAGCACGAAAAAAAAAAAAAAAAAAAAAAAA DOR25 (SEQ ID NO: 62)MNDSGYQSNLSLLRVFLDEFRSVLRQESPGLIPRLAFYYVRAFLSLPLYRWINLFIMCNVMTIFWTMFVALPESKNVIEMGDDLVWISGMALVFTKIFYMHLRCDEIDELISDFEYYNRELRPHNIDEEVLGWQRLCYVIESGLYINCFCLVNFFSAAIFLQPLLGEGKLPFHSVYPFQWHRLDLHPYTFWFLYIWQSLTSQHNLMSILMVDMVGISTFLQTALNLKLLCIEIRKLGDMEVSDKRFHEEFCRVVRFHQHIIKLVGKANRAFNGAFNAQLMASFSLISISTFETMAAAAVDPKMAAKFVLLMLVAFIQLSLWCVSGTLVYTQSVEVAQAAFDINDWHTKSPGIQRDISFVILRAQKPLMYVAEPFLPFTLGTYMLVLKNCYRLLALMQESM DOR25nt (SEQ ID NO:61) ATGAACGACTCGGGTTATCAATCAAATCTCAGCCTTCTGCGGGTTTTTCTCGACGAGTTCCGATCGGTTCTGCGGCAGGAAAGTCCCGGTCTCATCCCACGCCTGGCTTTTTACTATGTTCCCGCCTTTCTGAGCTTGCCCCTGTACCGATGGATCAACTTGTTCATCATGTGCAATGTGATGACCATTTTCTGGACCATGTTCGTGGCCCTGCCCGAGTCGAAGAACGTGATCGAAATGGGCGACGACTTGGTTTGGATTTCGGGGATGGCACTGGTGTTCACCAAGATCTTTTACATGCATTTGCGTTGCGACGAGATCGATGAACTTATTTCGGATTTTGAATACTACAACCGGGAGCTGAGACCCCATAATATCGATGAGGAGGTGTTGGGTTGGCAGAGACTGTGCTACGTGATAGAATCGGGTCTATATATCAACTGCTTTTGCCTGGTCAACTTCTTCAGTGCCGCTATTTTCCTGCAACCTCTGTTGGGCGAGGGAAAGCTGCCCTTCCACAGCGTCTATCCGTTTCAATGGCATCGCTTGGATCTGCATCCCTACACGTTCTGGTTCCTCTACATCTGGCAGAGTCTGACCTCGCAGCACAACCTAATGAGCATTCTAATGGTGGATATGGTAGGCATTTCCACGTTCCTCCAGACGGCGCTCAATCTCAAGTTGCTTTGCATCGAGATAAGGAAACTGGGGGACATGGAGGTCAGTGATAAGAGGTTCCACGAGGAGTTTTGTCGTGTGGTTCGCTTCCACCAGCACATTATCAAGTTGGTGGGGAAAGCCAATAGAGCTTTCAATGGCGCCTTCAATGCACAATTAATGGCCAGTTTCTCCCTGATTTCCATATCCACTTTCGAGACCATGGCTGCAGCGGCTGTGGATCCCAAAATGGCCGCCAAGTTCGTGCTTCTCATGCTGGTGGCATTCATTCAACTGTCGCTTTGGTGCGTCTCTGGAACTTTGGTTTATACTCAGTCAGTGGAGGTGGCTCAGGCTGCTTTTGATATCAACGATTGGCACACCAAATCGCCAGGCATCCAGAGGGATATATCCTTTGTGATACTACGAGCCCAGAAACCCCTGATGTATGTGGCCGAACCATTTCTGCCCTTCACCCTGGGAACCTATATGCTTGTACTGAAGAACTGCTATCGTTTGCTGGCCCTGATGCAAGAATCGATG TAG DOR28 (SEQ ID NO:64) MYSPEEAAELKRRNYRSIREMIRLSYTVGFNLLDPSRCGQVLRIWTIVLSVSSLASLYGHWQMLARYIHDIPRIGETAGTALQFLTSIAKMWYFLFAHRQIYELLRKARCHELLQKCELFERMSDLPVIKEIRQQVESTMNRYWASTRRQILIYLYSCICITTNYFINSFVINLYRYFTKPKGSYDIMLPLPSLYPAWEHKGLEFPYYHIQMYLETCSLYICGMCAVSFDGVFIVLCLHSVGLMRSLNQMVEQATSELVPPDRRVEYLRCCIYQYQRVANFATEVNNCFRHITFTQFLLSLFNWGLALFQMSVGLGNNSSITMIRMTMYLVAAGYQIVVYCYNGQRFATASEEIANAFYQVRWYGESREFRHLIRMMLMRTNRGFRLDVSWFMQMSLPTLMAVSSGAEQSRGPAGPAGPAGPPPRVPSYSQFHLIDSQMVRTSGQYFLLL QNVNQK DOR28nt (SEQID NO: 63) ATGTACTCACCGGAAGAGGCGGCCGAACTGAAGAGGCGCAACTATCGCAGCATCAGGGAGATGATCCGACTCTCCTATACGGTGGGCTTCAACCTGTTGGATCCTTCCCGATGCGGACAGGTGCTCAGAATCTGGACAATTGTCCTTAGCGTGAGTAGCTTGGCATCGCTTTATGGGCACTGGCAAATGTTAGCCAGGTACATTCATGATATTCCACGCATTGGAGAGACCGCTGGAACTGCCCTGCAGTTCCTAACATCGATAGCAAAGATGTGGTACTTTCTGTTTGCCCATAGACAGATATACGAATTGCTACGAAAGGCGCGCTGCCATGAATTACTCCAAAAGTGTGAGCTCTTTGAAAGGATGTCAGATCTACCTGTTATCAAAGAGATTCGCCAGCAGGTTGAGTCCACGATGAATCGGTACTGGGCCAGCACTCGTCGGCAAATTCTTATCTATTTGTACAGCTGTATTTGTATTACTACAAACTACTTTATCAACTCCTTCGTAATCAACCTCTATCGCTATTTCACTAAACCGAAAGGATCCTACGACATAATGTTACCTCTGCCATCTCTGTATCCCGCCTGGGAGCACAAGGGATTAGAGTTTCCCTACTATCATATACAGATGTACCTGGAAACCTGTTCTCTGTATATCTGCGGCATGTGTGCCGTTAGCTTTGATGGAGTCTTTATTGTCCTGTGCCTTCATAGCGTGGGACTTATGAGGTCACTTAACCAAATGGTGGAACAAGCCACATCTGAGTTGGTTCCTCCAGATCGCAGGGTTGAATACTTGCGATGCTGTATTTATCAGTACCAACGAGTGGCGAACTTTGCAACCGAGGTTAACAACTGCTTTCGGCACATCACTTTCACGCAGTTCCTGCTTAGCCTTTTCAACTGGGGCCTGGCCTTGTTCCAAATGAGCGTCGGATTGGGCAACAACAGCAGCATCACCATGATCCGGATGACCATGTACCTGGTGGCAGCCGGCTATCAGATAGTTGTGTACTGCTACAATGGCCAGCGATTTGCGACTGCTAGCGAGGAGATTGCCAACGCCTTTTACCAGGTGCGATGGTACGGAGAGTCCAGGGAGTTCCGCCACCTCATCCGCATGATGCTGATGCGCACGAACCGGGGATTCAGGCTGGACGTGTCCTGGTTCATGCAAATGTCCTTGCCCACACTCATGGCGGTGAGTAGCGGAGCAGAGCAGAGCAGGGGTCCTGCAGGTCCTGCAGGTCCTGCAGGTCCACCCCCAAGGGTCCCCTCCTACAGCCAGTTCCACTTGATTGATTCGCAGATGGTCCGGACAAGTGGACAGTACTTCCTGCTGCTG CAGAACGTCAACCAGAAADOR30 (SEQ ID NO: 66) MAVSTRVATKQEVPESRRAFRNLFNCFYALGMQAPDGSRPTTSSTWQRIYACFSVVMYVWQLLLVPTFFVISYRYMGGMEITQVLTSAQVAIDAVILPAKIVALAWNLPLLRRAEHHLAALDARCREQEEFQLILDAVRFCNYLVWFYQICYAIYSSSTFVCAFLLGQPPYALYLPGLDWQRSQMQFCIQAWIEFLIMNWTCLHQASDDVYAVIYLYVVRIQVQLLARRVEKLGTDDSGQVEIYPDERRQEEHCAELQRCIVDHQTMLQLLDCISPVISRTIFVQFLITAAIMGTTMINIFIFANTNTKIASIIYLLAVTLQTAPCCYQATSLMLDNERLALAIFQCQWLGQSARFRKMLLYYLHRAQQPITLTAMKLFPINLATYFSIAKFSFSLYTLI KGMNLGERFNRTN DOR30nt(SEQ ID NO: 65) ATGGCGGTGAGCACTCGTGTGGCCACAAAGCAGGAAGTGCCCGAATCCCGGCGAGCGTTTAGGAATCTCTTCAATTGCTTCTATGCCCTTGGCATGCAGGCACCGGATGGCAGTCGACCGACCACGAGCAGCACATGGCAACGCATCTACGCCTGCTTCTCGGTGGTCATGTACGTGTGGCAACTGCTGCTGGTGCCCACATTCTTTGTGATCAGCTATCGGTACATGGGCGGCATGGAGATTACCCAGGTGCTGACCTCCGCCCAGGTGGCCATCGATGCGGTCATTCTGCCGGCCAAGATTGTGGCACTGGCGTGGAATTTGCCATTGCTGCGCAGAGCAGAGCATCATCTGGCCGCCTTGGATGCGCGGTGCAGGGAACAGGAGGAGTTCCAATTGATCCTCGATGCGGTGAGGTTTTGCAACTATCTGGTATGGTTCTACCAGATCTGCTATGCCATCTACTCCTCGTCGACATTTGTGTGCGCCTTCCTGCTGGGCCAACCGCCATATGCCCTCTATTTGCCTGGCCTCGATTGGCAGCGTTCCCAGATGCAGTTCTGCATCCAGGCCTGGATTGAGTTCCTTATCATGAACTGGACGTGCCTGCACCAAGCTAGCGATGATGTGTACGCCGTTATCTATCTGTATGTGGTCCGGATTCAAGTGCAATTGCTGGCCAGGCGGGTGGAGAAGCTGGGCACGGATGATAGTGGCCAGGTGGAGATCTATCCCGATGAGCGGCGGCAGGAGGAGCATTGCGCGGAACTGCAGCGCTGCATTGTAGATCACCAGACGATGCTGCAGCTGCTCGACTGCATTAGTCCCGTCATCTCGCGTACCATATTCGTTCAGTTCCTGATCACCGCCGCCATCATGGGCACCACCATGATCAACATTTTCATTTTCGCCAATACGAACACGAAGATCGCATCGATCATTTACCTGCTGGCGGTGACCCTGCAGACGGCTCCATGTTGCTATCAGGCCACCTCGCTGATGTTGGACAACGAGAGGCTGGCCCTGGCCATCTTCCAGTGCCAGTGGCTGGGCCAGAGTGCCCGGTTCCGTAAGATGCTGCTCTACTATCTTCATCGCGCCCAGCAGCCCATCACGCTGACCGCCATGAAGCTGTTTCCCATCAATCTGGCCACGTACTTCAGTATAGCCAAGTTCTCGTTTTCGCTCTACACGCTCATCAAGGGGATGAATCTCGGCGAGCGATTCAACAGGACAAAT DOR31 (SEQ ID NO: 68)MIFKYIQEPVLGSLFRSRDSLIYLNRSIDQMGWRLPPRTKPYWWLYYIWTLVVIVLVFIFIPYGLIMTGIKEFKNFTTTDLFTYVQVPVNTNASIMKGIIVLFMRRRFSRAQKMMDAMDIRCTKMEEKVQVHRAAALCNRVVVIYHCIYFGYLSMALTGALVIGKTPFCLYNPLVNPDDHFYLATAIESVTMAGIILANLILDVYPIIYVVVLRIHMELLSERIKTLRTDVEKGDDQHYAELVECVKDHKLIVEYGNTLRPMISATMFIQLLSVGLLLGLAAVSMQFYNTVMERVVSGVYTIAILSQTFPFCYVCEQLSSDCESLTNTLFHSKWIGAERRYRTTMLYFIHNVQQSILFTAGGIFPICLNTNIKMAKFAFSVVTIVNEMDLAEKLRRE DOR31nt (SEQ ID NO: 67)ATGATTTTTAAGTACATTCAAGAGCCAGTCCTTGGATCCTTATTTCGATCCCGGGATTCGCTGATCTACTTAAACAGATCCATAGATCAAATGGGATGGAGACTGCCGCCACGAACTAAGCCGTACTGGTGGCTCTATTACATTTGGACATTGGTGGTCATAGTACTCGTCTTTATCTTTATACCCTATGGACTGATAATGACTGGAATAAAGGAGTTCAAGAACTTCACGACCACGGATCTGTTTACGTATGTCCAGGTGCCGGTTAACACCAATGCTTCGATCATGAAGGGCATTATAGTGTTGTTTATGCGGCGGCGATTTTCAAGGGCTCAGAAGATGATGGACGCCATGGACATTCGATGCACCAAGATGGAGGAGAAAGTCCAGGTGCACCGAGCAGCAGCCTTATGCAATCGTGTTGTTGTGATTTACCATTGCATATACTTCGGCTATCTATCCATGGCCTTAACCGGAGCTCTGGTGATTGGGAAGACTCCATTCTGTTTGTACAATCCACTGGTTAACCCCGACGATCATTTCTATCTGGCCACTGCCATTGAATCGGTCACCATGGCTGGCATTATTCTGGCCAATCTCATTTTGGACGTATATCCCATCATATATGTGGTCGTTCTGCGGATCCACATGGAGCTCTTGAGTGAGCGAATCAAGACGCTGCGTACTGATGTGGAAAAAGGCGACGATCAACATTATGCCGAGCTGGTGGAGTGTGTAAAGGATCACAAGCTAATTGTCGAATATGGAAACACTCTGCGTCCCATGATATCCGCCACGATGTTCATCCAACTACTATCCGTTGGCTTACTTTTGGGTCTGGCAGCGGTGTCCATGCAGTTCTATAACACCGTAATGGAGCGTGTTGTCTCCGGGGTCTACACCATAGCCATTCTATCCCAGACCTTTCCATTTTGCTATGTCTGTGAGCAGCTGAGCAGCGATTGCGAATCCCTGACCAACACACTGTTCCATTCCAAGTGGATTGGAGCTGAGCGACGATACAGAACCACGATGTTGTACTTCATTCACAATGTTCAGCAGTCGATTTTGTTCACTGCGGGCGGAATTTTCCCCATATGTCTAAACACCAATATAAAGATGGCCAAGTTCGCTTTCTCAGTGGTGACCATTGTAAATGAGATGGACTTGGCCGAGAAATTGAGAAGGGAG DOR32 (SEQ ID NO: 68)MEPVQYSYEDFARLPTTVFWIMGYDMLGVPKTRSRRILYWIYRFLCLASHGVCVGVMVFRMVEAKTIDNVSLIMRYATLVTYIINSDTKFATVLQRSAIQSLNSKLAELYPKTTLDRIYHRVNDHYWTKSFVYLVIIYIGSSIMVVIGPIITSIIAYFTHNVFTYMHCYPYFLYDPEKDPVWIYISIYALEWLHSTQMVISNIGADIWLLYFQVQINLHFRGIIRSLADHKPSVKHDQEDRKFIAKIVDKQVHLVSLQNDLNGIFGKSLLLSLLTTAAVICTVAVYTLIQGPTLEGFTYVIFIGTSVMQVYLVCYYGQQVLDLSGEVAHAVYNHDFHDASIAYKRYLLIIIIRAQQPVELNAMGYLSISLDTFKQLMSVSYRVITMLMQMIQ DOR32nt (SEQ ID NO: 61)ATGGAACCTGTGCAGTACAGCTACGAGGATTTCGCTCGATTGCCCACGACGGTGTTCTGGATCATGGGCTACGACATGCTGGGCGTTCCGAAGACCCGCTCTCGCAGGATACTATACTGGATATATCGTTTCCTCTGTCTCGCCAGCCATGGGGTCTGTGTAGGAGTCATGGTATTTCGTATGGTGGAGGCAAAGACCATTGACAATGTTTCGCTGATCATGCGGTATGCCACTCTGGTCACCTATATCATCAACTCGGATACGAAATTCGCAACTGTCTTACAAAGGAGTGCAATTCAAAGTCTAAACTCAAAACTGGCCGAACTATATCCGAAGACCACGCTGGACAGGATCTATCACCGGGTGAATGATCACTATTGGACCAAGTCATTTGTATATTTGGTTATTATCTACATTGGTTCGTCGATTATGGTTGTTATTGGACCGATTATTACGTCGATTATAGCTTACTTCACGCACAACGTTTTCACCTACATGCACTGCTATCCGTACTTTTTGTATGATCCTGAGAAGGATCCGGTTTGGATCTACATCAGCATCTATGCTCTGGAATGGTTGCACAGCACACAGATGGTCATTTCGAACATTGGCGCGGATATCTGGCTGCTGTACTTTCAGGTGCAGATAAATCTCCACTTCAGGGGCATTATACGATCACTGGCGGATCACAAGCCCAGTGTGAAGCACGACCAGGAGGACAGGAAATTCATTGCGAAAATTGTCGACAAGCAGGTGCACCTGGTCAGTTTGCAAAACGATCTGAATGGTATCTTTGGAAAATCGCTGCTTCTAAGCCTGCTGACCACCGCAGCGGTTATCTGCACGGTGGCGGTGTACACTCTGATTCAGGGTCCCACCTTGGAGGGCTTCACCTATGTGATCTTCATCGGGACTTCTGTGATGCAGGTCTACCTGGTGTGCTATTACGGTCAGCAAGTTCTCGACTTGAGCGGCGAGGTGGCCCACGCCGTGTACAATCATGATTTTCACGATGCTTCTATAGCGTACAAGAGGTACCTGCTCATAATCATTATCAGGGCGCAGCAGCCCGTGGAACTTAATGCCATGGGCTACCTGTCCATTTCGCTGGACACCTTTAAACAGCTGATGAGCGTCTCCTACCGGGTTATAACCATGCTCATGCAGATGATTCAG DOR37 (SEQ ID NO: 110) (protein sequence isincomplete) KVDSTRALVNHWRIFRIMGIHPPGKRTFWGRHYTAYSMVWNVTFHICIWVSFSVNLLQSNSLETFCESLCVTMPHTLYMLKLINVRRMRGQMISSHWLLRLLDKRLGCDDERQIIMAGIERAEFIFRTIFRGLACTVVLGIIYISASSEPTLMYPTWIPWNWRDSTSAYLATAMLHTTALMANATLVLNLSSYPGTYLILVSVHTKALALRVSKLGYGAPLPAVRMQAILVGYIHDHQIILR*VSGNLISQCKNF*SISGVLTFIERRMYTHFGVPNIFIVIEDYYILFLNYSLFKSLERSLSMTCFLQFFSTACAQCTICYFLLFGNVGIMRFMNMLFLLVILTTETLLLCYTAELPCKEGESLLTAVYSCNWLSQSVNFRRLLLLMIARCQIPMILVS GVIVPISMKTF DOR38(SEQ ID NO: 72) MRLIKISYSALNEVCVWLKLNGSWPLTESSRPWRSQSLLATAYIVWAWYVIASVGITISYQTAFLLNNLSDIIITTENCCTTFMGVLNFVRLIHLRLNQRKFRQLIENFSYEIWIPNSSKNNVAAECRRRMVTFSIMTSLLACLIIMYCVLPLVEIFFGPAFDAQNKPFPYKMIFPYDAQSSWIRYVMTYIFTSYAGICVVTTLFAEDTILGFFITYTCGQFHLLHQRIAGLFAGSNAELAESIQLERLK RIVEKHNNIISANSVDOR38nt (SEQ ID NO: 71)ATGCGTTTGATCAAAATTTCATATTCGGCACTTAATGAGGTGTGCGTTTGGCTGAAACTGAATGGTTCTTGGCCATTAACCGAATCATCGAGGCCATGGAGGAGCCAATCCTTATTGGCCACCGCCTACATCGTGTGGGCGTGGTACGTCATTGCATCTGTGGGCATAACAATCAGCTATCAGACGGCCTTTTTGCTGAACAACCTTTCGGACATTATTATCACCACGGAAAATTGTTGCACCACCTTTATGGGTGTCCTGAACTTTGTCCGACTCATCCATCTTCGCCTCAATCAGAGGAATTCCGCCAGCTTATTGAGAACTTTTCCTACGAAAATTTGGATACCTAATTCTTCCAAAAACAATGTTGCCGCCGAGTGTCGCAGACGCATGGTTACCTTCAGCATAATGACATCCTTGCTAGCGTGCCTGATCATAATGTATTGTGTCCTGCCGCTGGTGGAGATCTTCTTTGGACCCGCCTTCGATGCACAGAACAAGCCGTTTCCCTACAAGATGATCTTTCCGTACGATGCCCAGAGCAGTTGGATCCGATATGTGATGACCTACATCTTCACCTCCTACGCGGGAATCTGTGTGGTCACCACCTTGTTTGCAGAGGACACCATTCTTGGCTTCTTCATAACCTACACTTGTGGCCAATTTCATTTGCTACACCAACGAATCGCAGGTTTATTTGCGGGTTCCAATGCGGAATTGGCCGAGAGCATTCAGCTGGAGCGACTCAAACGTATTGTGGAAAAACACAACAATATTATCAGCGCAAATTCTGTA DOR44 (SEQ ID NO: 106)MKSTFKEERIKDDSKRRDLFVFVRQTMCIAAMYPFGYYVNGSGVLAVLVRFCDLTYELFNYFVSVHIAGLYICTIYINYGQGDLDFFVNCLIQTIIYLWTIAMKLYFRRFRPGLLNTILSNINDEYETRSAVGFSFVTMAGSYRMSKLWIKTYVYCCYIGTIFWLALPIAYRDRSLPLACWYPFDYTQPGVYEVVFLLQAMGQIQVAASFASSSGLHMVLCVLISGQYDVLFCSLKNVLASSYVLMGANMTELNQLQAEQSAADVEPGQYAYSVEEETPLQELLKVGSSMDFSSAFRLSFVRCIQHHRYIVAALKKIESFYSPIWFVKIGEVTFLMCLVAFVSTKSTAANSFMRMVSLGQYLLLVLYELFIICYFADIVFQNSQRCGEALWRSPWQRHLKDVRSDYMFFMLNSRRQFQLTAGKISNLNVDRFRGVGILT DOR44nt (SEQ ID NO: 105)ATGAAGAGCACATTCAAGGAAGAAAGGATTAAGGACGACTCCAAGCGTCGCGACCTGTTTGTATTCGTGAGGCAAACCATGTGTATAGCGGCCATGTATCCCTTCGGTTACTACGTGAATGGATCTGGAGTCCTGGCCGTTCTGGTGCGATTCTGTGACTTGACCTACGAGCTCTTTAACTACTTCGTTTCGGTACACATAGCTGGCCTGTACATCTGCACCATCTACATCAACTATGGGCAAGGCGATTTGGACTTCTTCGTGAACTGTTTGATACAAACCATTATTTATCTGTGGACAATAGCGATGAAACTCTACTTTCGGAGGTTCAGACCTGGTTTGTTGAATACCATTCTGTCCAACATCAATGATGACTACGAGACACGTTCGGCTGTGGGATTCAGTTTCGTCACAATGGCGGGATCCTATCGGATGTCCAAGCTATGGATCAAAACCTATGTGTATTGCTGCTACATAGGCACCATTTTCTGGCTGGCTCTTCCCATTGCCTACCGGGATAGGAGTCTTCCTCTTGCCTGCTGGTATCCCTTTGACTATACACAACCCGGTGTCTATGAGGTAGTGTTCCTTCTCCAGGCGATGGGACAGATCCAAGTGGCCGCATCCTTTGCCTCCTCCAGTGGCCTGCATATGGTGCTTTGTGTGCTGATATCAGGGCAGTACGATGTCCTCTTTTGCAGTCTCAAGAATGTATTAGCCAGCAGCTATGTCCTTATGGGAGCCAATATGACGGAACTGAATCAATTGCAGGCTGAGCAATCTGCGGCCGATGTCGAGCCAGGTCAGTATGCTTACTCCGTGGAGGAGGAGACACCTTTGCAAGAACTTCTAAAAGTTGGGAGCTCAATGGACTTCTCCTCCGCATTCAGGCTGTCTTTTGTGCGGTGCATTCAGCACCATCGATACATAGTGGCGGCACTGAAGAAAATTGAGAGTTTCTACAGTCCCATATGGTTCGTGAAGATTGGCGAAGTCACCTTTCTTATGTGCCTGGTAGCCTTCGTCTCCACGAAGAGCACCGCGGCCAACTCATTCATGCGAATGGTCTCCTTGGGCCAGTACCTGCTCTTAGTTCTCTACGAGCTGTTCATCATCTGCTACTTCGCGGACATCGTTTTTCAGAACAGCCAGCGGTGCGGTGAAGCCCTCTGGCGAAGTCCTTGGCAGCGACATTTGAAGGATGTTCGCAGTGATTACATGTTCTTTATGCTGAATTCCCGCAGGCAGTTCCAACTTACGGCCGGAAAAATAAGCAATCTAAACGTGGATCGTTTCAGAG GGGTGGGTATCCTTACTDOR46 (SEQ ID NO: 20) MAEVRVDSLEFFKSHWTAWRYLGVAHFRVENWKNLYVFYSIVSNLLVTLCYPVHLGISLFRNRTITEDILNLTTFATCTACSVKCLLYAYNIKDVLEMERLLRLLDERVVGPEQRSIYGQVRVQLRNVLYVFIGIYMPCALFAELSFLFKEERGLMYPAWFPFDWLHSTRNYYIANAYQIVGISFQLLQNYVSDCFPAVVLCLISSHIKMLYNRFEEVGLDPARDAEKDLEACITDHKHILELFRRIEAFISLPMLIQFTVTALNVCIGLAALVFFVSEPMARMYFIFYSLAMPLQIFPSCFFGTDNEYWFGRLHYAAFSCNWHTQNRSFKRKMMLFVEQSLKKSTAVAGGMMRIHLDTFFSTLKGAYSLFTIIIRMRK DOR46nt (SEQ ID NO: 19)ATGGCAGAGGTCAGAGTGGACAGTCTGGAGTTTTTCAAGAGCCATTGGACCGCCTGGCGGTACTTGGGAGTGGCTCATTTTCGGGTCGAGAACTGGAAGAACCTTTACGTGTTTTACAGCATTGTGTCGAATCTTCTCGTGACCCTGTGCTACCCCGTTCACCTGGGAATATCCCTCTTTCGCAACCGCACCATCACCGAGGACATCCTCAACCTGACCACCTTTGCGACCTGCACAGCCTGTTCGGTGAAGTGCCTGCTCTACGCCTACAACATCAAGGATGTGCTGGAGATGGAGCGGCTGTTGAGGCTTTTGGATGAACGCGTCGTGGGTCCGGAGCAACGCAGCATCTACGGACAAGTGAGGGTCCAGCTGCGAAATGTGCTATACGTGTTCATCGGCATCTACATGCCGTGTGCCCTGTTCGCCGAGCTATCCTTTCTGTTCAAGGAGGAGCGCGGTCTGATGTATCCCGCCTGGTTTCCCTTCGACTGGCTGCACTCCACCAGGAACTATTACATAGCGAACGCCTATCAGATAGTGGGCATCTCGTTTCAGCTGCTGCAAAACTATGTTAGCGACTGCTTTCCGGCGGTGGTGCTGTGCCTGATCTCATCCCACATCAAAATGTTGTACAACAGATTCGAGGAGGTGGGCCTGGATCCAGCCAGAGATGCGGAGAAGGACCTGGAGGCCTGCATCACCGATCACAAGCATATTCTAGAGTGGGCAGGCGGCTCATTGGTTCGTGTTCTATTCACTTTCCAACTTTTTTCCAGACTATTCCGACGCATCGAGGCCTTCATTTCCCTGCCCATGCTAATTCAGTTCACAGTGACCGCCTTGAATGTGTGCATCGGTTTAGCAGCCCTGGTGTTTTTCGTCAGCGAGCCCATGGCACGGATGTACTTCATCTTCTACTCCCTGGCCATGCCGCTGCAGATCTTTCCGTCCTGCTTTTTCGGCACCGACAACGAGTACTGGTTCGGACGCCTCCACTACGCGGCCTTCAGTTGCAATTGGCACACACAGAACAGGAGCTTTAAGCGGAAAATGATGCTGTTCGTTGAGCAATCGTTGAAGAAGAGCACCGCTGTGGCTGGCGGAATGATGCGTATCCACCTGGACACGTTCTTTTCCACCCTAAAGGGGGCCTACTCCCTCTTTACCATCATTATTCGGATGAGAAAG DOR48 (SEQ ID NO: 26)MERHYFMVPKFALSLIGFYPEQKRTVLVKLWSFFNFFILTYGCYAEAYYGIHYIPINIATALDALCPVASSILSLVKMVAIWWYQDELRSLIERRFYTLATQLTFLLLCCGFCTSTSYSVRHLIDNILRRTHGKDWIYETPFKMMFPDLLLRLPLYPITYILVHWHGYITVVCFVGADGFFLGFCLYFTVLLLCLQDDVCDLLEVENIEKSPSEAEEARIVREMEKLVDRHNEVAELTERLSGVMVEITLAHFVTSSLIIGTSVVDILLFSGLGIIVYVVYTCAVGVEIFLYCLGGSHIMEACSNLARSTFSSHWYGHSVRVQKMTLLMVARAQRVLTIKIPFFSPSLET LTSILRFTGSLIALAKSVIDOR48nt (SEQ ID NO: 25)ATGGAGCGCCATTATTTCATGGTGCCAAAGTTTGCATTATCGCTGATTGGTTTTTATCCCGAACAGAAGCGAACGGTTTTGGTGAAACTTTGGAGTTTCTTCAACTTTTTCATCCTCACCTACGGCTGTTATGCAGAGGCTTACTATGGCATACACTATATACCGATTAACATAGCCACTGCATTGGATGCCCTTTGTCCTGTGGCCTCCAGCATTTTGTCGCTGGTGAAAATGGTCGCCATTTGGTGGTATCAAGATGAATTAAGGAGTTTGATAGAGCGGGTAAGATTTTTAACAGAGCAACAGAAGTCCAAGAGGAAACTGGGCTATAAGAAGAGGTTCTATACACTGGCAACGCAACTAACATTCCTGCTACTATGCTGTGGATTTTGCACCAGTACTTCCTATTCCGTCAGACATTTGATTGATAATATCCTGAGACGCACCCATGGCAAGGACTGGATCTACGAGACTCCGTTCAAGATGATGTAAGGAAAGGGAAGAATGGTTTATATATACTTTTGGAACGAAATAATGATGTGATCTAAACAAGATGCACTTTTTTTTAGGTTCCCCGATCTTCTCCTGCGTTTGCCACTCTATCCCATCACCTATATACTCGTGCATTGGCATGGCTACATTACTGTGGTTTGTTTTGTCGGCGCGGATGGTTTCTTCCTGGGGTTCTGTTTGTACTTCACTGTTTTGCTGCTCTGTCTGCAGGACGATGTTTGTGATTTACTAGAGGTTGAAAACATCGAGAAGAGTCCCTCCGAAGCGGAGGAAGCTCGCATAGTTCGGGAAATGGAAAAACTGGTGGACCGGCATAACGAGGTGGCCGAGCTGACAGAAAGATTGTCGGGTGTTATGGTGGAAATAACACTGGCCCACTTTGTTACTTCGAGTTTGATAATCGGAACCAGCGTGGTGGATATTTTATTAGTGGGTATTTACATTTGATTAGATCCTTTCGATATATGTTCTTAAATTCTAGTTTTCCGGCCTGGGAATCATTGTGTATGTGGTCTACACTTGTGCCGTAGGTGTGGAAATATTTCTATACTGTTTAGGAGGATCTCATATTATGGAAGCGGTATATTCATAAGAAACTACTATAAAGTTACTTTTAAATTCATTGCATTTCTTAGTGTTCCAATCTAGCGCGCTCCACATTTTCCAGCCACTGGTATGGCCACAGTGTTCGGGTCCAAAAGATGACCCTTTTGATGGTAGCTCGTGCTCAACGAGTTCTCACAATTAAAATTCCTTTCTTTTCCCCATCATTAGAGACTCTAACTTCGGTAAGCTTATGCGAAAATGTTATGGTACACACAAGTCTACATTTCTATGAGGTCTTGTAGATTTTGCGCTTCACTGGATCTCTGATTGCCCTGGCAAAG TCGGTTATA DOR53 (SEQID NO: 8) MLSKFFPHIKEKPLSERVKSRDAFIYLDRVMWSFGWTEPENKRWILPYKLWLAFVNIVMLILLPISISIEYLHRFKTFSAGEFLSSLEIGVNMYGSSFKCAFTLIGFKKRQEAKVLLDQLDKRCLSDKERSTVHRYVAMGNFFDILYHIFYSTFVVMNFPYFLLERRHAWRMYFPYIDSDEQFYISSIAECFLMTEAIYMDLCTDVCPLISMLMARCHISLLKQRLRNLRSKPGRTEDEYLEELTECIRDHRLLLDYVDALRPVFSGTIFVQFLLIGTVLGLSMINLMFFSTFWTGVATCLFMFDVSMETFPFCYLCNMIIDDCQEMSNCLFQSDWTSADRRYKSTLVYFLHNLQQPITLTAGGVFPISMQTNLAMVKLAFSVVTVIKQFNLAERFQ DOR53nt (SEQ ID NO: 7)TCAAACAAAGCCACGGACAAGATGTTAAGCAAGTTTTTTCCCCACATAAAAGAAAAGCCATTGAGCGAGCGGGTTAAGTCCCGAGATGCCTTCATTTACTTGGATCGGGTGATGTGGTCCTTTGGCTGGACAGAGCCTGAAAACAAAAGGTGGATCCTTCCTTATAAACTGTGGTTAGCGTTCGTGAACATAGTAATGCTCATCCTTCTGCCGATCTCGATAAGCATCGAGTACCTCCACCGATTTAAAACCTTCTCGGCGGGGGAGTTCCTTAGTTCCCTCGAGATTGGAGTCAACATGTACGGAAGCTCTTTTAAGTGCGCCTTCACCTTGATTGGATTCAAGAAAAGACAGGAAGCTAAGGTTTTACTGGATCAGCTGGACAAGAGATGCCTTAGCGATAAGGAGAGGTCCACTGTTCATCGCTATGTCGCCATGGGAAACTTTTTCGATATTTTGTATCACATTTTTTACTCCACCTTCGTGGTAATGAACTTCCCGTATTTTCTGCTTGAGAGACGCCATGCTTGGCGCATGTACTTTCCATATATCGATTCCGACGAACAGTTTTACATCTCCAGCATCGCCGAGTGTTTTCTGATGACGGAGGCCATCTACATGGATCTCTGTACGGACGTGTGTCCCTTGATCTCCATGCTTATGGCTCGATGCCACATCAGCCTCCTGAAACAGCGACTGAGAAATCTCCGATCGAAGCCAGGAAGGACCGAAGATGAGTACTTGGAGGAGCTCACCGAGTGCATTCGGGATCATCGATTGCTATTGGACTATGTTGACGCATTGCGACCCGTCTTTTCGGGAACCATTTTTGTGCAGTTCCTCCTGATCGGTACTGTACTGGGTCTCTCAATGATAAATCTAATGTTCTTCTCGACATTTTGGACTGGTGTCGCCACTTGCCTTTTTATGTTCGACGTGTCCATGGAGACGTTCCCCTTTTGCTATTTGTGCAACATGATTATCGATGACTGCCAGGAAATGTCCAATTGCCTCTTTCAATCGGACTGGACCTCTGCCGATCGTCGCTACAAATCCACTTTGGTATACTTTCTTCACAATCTTCAGCAACCCATTACTCTCACGGCTGGTGGAGTGTTTCCTATTTCCATGCAAACAAATTTGGCTATGGTGAAGCTGGCATTTTCTGTGGTTACGGTAATTAAGCAATTTAACTTGGCCGAAAGGTTTCAATAAGTTGAGAGGGACGAGCTCTGCTACTATTATATTATATATTATATTATATTATATATATATTATTTTATATTATATATTGCTGTACCCTAATAAATATTTAGTAATAAAAAAAAAAAAAAAAAA DOR56 (SEQ ID NO: 76)MDPVEMPIFGSTLKLMKFWSYLFVHNWRRYVAMTPYIIINCTQYVDIYLSTESLDFIIRNVYLAVLFTNTVVRGVLLCVQRFSYERFINILKSFYIELLVSTERLSQKCILHKWAVLPYGMYLPTIDEYKYASPYYEIFFVIQAIMAPMGCCMYIPYTNMVVTFTLFAILMCRVLQHKLRSLEKLKNEQVRGEIAQTIAQTVIVIAYMVMIFANSVVLYYVANELYFQSFDIAIAAYESNWMDFDVDTQKTLKFLIMRSQKPLASLVGGTYPMNLKMLQSLLNAIYSFFTLLRRVYG DOR56nt (SEQ ID NO: 75)ATGGATCCGGTGGAGATGCCCATTTTTGGTAGCACTCTGAAGCTAATGAAGTTCTGGTCATATCTGTTTGTTCACAACTGGCGCCGCTATGTCGCAATGACTCCGTACATCATTATCAACTGTACTCAGTATGTGGATATATATCTGAGCACCGAATCCTTGGACTTTATCATCAGAAATGTATACCTGGCTGTATTGTTTACCAACACGGTGGTCAGAGGTGTATTGTTATGCGTACAGCGGTTTAGCTACGAGCGTTTCATTAATATTTTGAAAAGCTTTTACATTGAGTTGTTGGTGAGTACCGAAAGATTATCTCAAAAATGCATATTGCATAAATGGGCAGTTCTGCCATATGGCATGTATTTGCCCACTATTGATGAATACAAATACGCATCACCTTACTACGAGATTTTCTTTGTGATTCAAGCCATTATGGCTCCAATGGGGTGTTGCATGTACATACCATACACAAACATGGTAGTGACATTTACCCTTTTCGCCATTCTCATGTGTCGAGTGTTGCAACATAAGTTGAGAAGCCTAGAAAAGCTGAAAAATGAACAAGTACGTGGTGAAATCGCTCAAACAATTGCTCAGACCGTCATAGTCATCGCATACATGGTAATGATATTTGCCAACAGTGTAGTCCTTTACTACGTGGCCAATGAGCTATACTTTCAAAGCTTTGATATTGCCATTGCTGCCTATGAGAGCAATTGGATGGACTTTGATGTGGACACACAAAAGACTTTGAAGTTCCTCATCATGCGCTCGCAAAAGCCCTTGGCGAGTCTGGTGGGTGGCACATATCCCATGAACTTGAAAATGCTTCAGTCACTACTAAATGCCATTTACTCCTTCTTCACCCTTCTGCGTCGCGTTTACGGC DOR58 (SEQ ID NO: 78)MDASYFAVQRRALEIVGFDPSTPQLSLKHPIWAGILILSLISHNWPMVVYALQDLSDLTRLTDNFAVFMQGSQSTFKFLVMMAKRRRIGSLIHRLHKLNQAASATPNHLEKIERENQLDRYVARSFRNAAYGVICASAIAPMLLGLWGYVETGVFTPTTPMEFNFWLDERKPHFYWPIYVWGVLGVAAAAWLAIATDTLFSWLTHNVVIQFQLLELVLEEKDLNGGDSRLTGFVSRHRIALDLAKELSSIFGEIVFVKYMLSYLQLCMLAFRFSRSGWSAQVPFRATFLVAIIIQLSSYCYGGEYIKQQSLAIAQAVYGQINWPEMTPKKRRLWQMVIMRAQRPAKIFGFMFVVDLPLLLWVIRTAGSFLAMLRTFER DOR58nt (SEQ ID NO: 77)ATGGACGCCAGCTACTTTGCCGTCCAGAGAAGAGCTCTGGAAATAGTTGGATTCGATCCCAGTACTCCGCAACTGAGTCTGAAACATCCCATCTGGGCCGGGATTCTCATCCTGTCCTTGATCTCTCACAACTGGCCCATGGTAGTCTATGCCCTGCAGGATCTCTCCGACTTGACCCGTCTGACGGACAACTTTGCGGTGTTTATGCAAGGATCACAGAGCACCTTCAAGTTCCTGGTCATGATGGCGAAACGAAGGCGCATTGGATCGTTGATTCACCGTTTGCATAAGCTAAACCAGGCGGCCAGTGCCACGCCCAATCACCTGGAGAAGATCGAGAGGGAAAACCAACTGGATAGGTATGTCGCCAGGTCCTTTAGAAATGCCGCCTACGGAGTGATTTGTGCCTCGGCCATAGCGCCCATGTTGCTTGGCCTGTGGGGATATGTGGAGACGGGTGTATTTACCCCCACCACACCCATGGAGTTCAACTTCTGGCTGGACGAGCGAAAGCCTCACTTTTATTGGCCCATCTACGTTTGGGGCGTACTGGGCGTGGCAGCTGCCGCCTGGTTGGCCATTGCAACGGACACCCTGTTCTCCTGGCTGACTCACAATGTGGTGATTCAGTTCCAACTACTGGAGCTTGTTCTCGAAGAGAAGGATCTGAATGGCGGAGACTCTCGCCTGACCGGGTTTGTTAGTCGTCATCGTATAGCTCTGGATTTGGCCAAGGAACTAAGTTCGATTTTCGGGGAGATCGTCTTTGTGAAATACATGCTCAGTTACCTGCAACTCTGCATGTTGGCCTTTCGCTTCAGCCGCAGTGGCTGGAGTGCCCAGGTGCCATTTAGAGCCACCTTCCTAGTGGCCATCATCATCCAACTGAGTTCGTATTGCTATGGAGGCGAGTATATAAAGCAGCAAAGTTTGGCCATCGCACAAGCCGTTTATGGTCAAATCAATTGGCCAGAAATGACGCCAAAGAAAAGAAGACTCTGGCAAATGGTGATCATGAGGGCGCAGCGACCGGCTAAGATTTTTGGATTCATGTTCGTTGTGGACTTGCCACTGCTGCTTTGGGTCATCAGAACTGCGGGCTCATTTCTGGCCATGCTTAGGACTTTCGAGCGT DOR59 (SEQ ID NO: 80)MHEADNREMELLVATQAYTRTITLLIWIPSVIAGLMAYSDCIYRSLFLPKSVFNVPAVRRGEEHPILLFQLFPFGELCDNFVVGYLGPWYALGLGITAIPLWHTFITCLMKYVNLKLQILNKRVEEMDITRLNSKLVIGRLTASELTFWQMQLFKEFVKEQLRIRKFVQELQYLICVPVMADFIIFSVLICFLFFALTVGHDELSLAYFSCGWYNFEMPLQKMLVFMMMHAQRPMKMRALLVDLNLRTFI DIGRGAYSYFNLLRSSHLYDOR59nt (SEQ ID NO: 79)ATGCACGAAGCAGATAATCGGGAGATGGAACTTTTGGTCGCCACTCAGGCTTATACACGAACCATTACCCTGTTGATCTGGATACCATCGGTTATTGCTGGCCTAATGGCCTATTCAGACTGCATCTACAGGAGTCTGTTTCTGCCGAAATCGGTTTTCAATGTGCCAGCTGTGCGACGTGGTGAGGAGCATCCCATTCTGCTATTTCAGCTGTTTCCCTTCGGAGAACTTTGCGATAACTTCGTTGTTGGATACTTGGGACCTTGGTATGCTCTGGGCCTGGGAATCACGGCTATCCCATTGTGGCACACCTTTATCACTTGCCTCATGAAGTACGTAAATCTCAAGCTGCAAATACTCAACAAGCGAGTGGAGGAGATGGATATTACCCGACTTAATTCCAAATTGGTAATTGGTCGCCTAACTGCCAGTGAGTTAACCTTCTGGCAAATGCAACTCTTCAAGGAATTTGTAAAGGAACAGCTGAGGATTCGAAAATTTGTCCAGGAACTACAGTATCTGATTTGCGTGCCTGTGATGGCAGATTTCATTATCTTCTCGGTTCTCATTTGCTTTCTCTTTTTTGCCTTGACAGTTGGCCACGATGAACTGAGCCTTGCTTACTTTTCTTGCGGATGGTACAACTTCGAAATGCCTTTGCAGAAAATGCTGGTTTTTATGATGATGCATGCCCAAAGGCCGATGAAGATGCGCGCCCTGCTGGTCGATTTGAATCTGAGGACCTTCATAGACATTGGCCGTGGAGCCTACAGCTACTTCAATTTGCTGCGTAGCTCCCA CTTGTAT DOR61 (SEQ IDNO: 108) MGHKDDMDSTDSTALSLKHISSLIFVISAQYPLISYVAYNRNDMEKVTACLSVVFTNMLTVIKISTFLANRKDFWEMIHRFRKMHEQCKYREGLDYVAEANKLASFLGRAYCVSCGLTGLYFMLGPIVKIGVCRWHGTTCDKELPMPMKFPFNDLESPGYEVCFLYTVLVTVVVVAYASAVDGLFISFAINLRAHFQTLQRQIENWEFPSSEPDTQIRLKSIVEYHVLLLSLSRKLRSIYTPTVMGQFVITSLQVGVIIYQLVTNMDSVMDLLLYASFFGSIMLQLFIYCYGGEIIKAESLQVDTAVRLSNWHLASPKTRTSLSLIILQSQKEVLIRAGFFVASLANFPY RLITLIKSIDSIC DOR62(SEQ ID NO: 2) MEKQEDFKLNTHSAVYYHWRVWELTGLMRPPGVSSLLYVVYSITVNLVVTVLFPLSLLARLLFTTNMAGLCENLTITITDIVANLKFANVYMVRKQLHEIRSLLRLMDARARLVGDPEEISALRKEVNIAQGTFRTFASIFVFGTTLSCVRVVVRPDRELLYPAWFGVDWMHSTRNYVLINIYQLFGLIVQAIQNCASDSYPPAFLCLLTGHMRALELRVRRIGCRTEKSNKGQTYEAWREEVYQELIECIRDLARVHRLREIIQRVLSVPCMAQFVCSAAVQCTVAMHFLYVADDHDHTAMIISIVFFSAVTLEVFVICYFGDRMRTQSEALCDAFYDCNWIEQLPKFKRELLFTLARTQRPSLIYAGNYIALSLETFEQVMRFTYSVFTLLLRAK DOR62nt (SEQ ID NO: 1)ATGGAGAAGCAAGAGGATTTCAAACTGAACACCCACAGTGCTGTGTACTACCACTGGCGCGTTTGGGAGCTCACTGGCCTGATGCGTCCTCCGGGCGTTTCAAGCCTGCTTTACGTGGTATACTCCATTACGGTCAACTTGGTGGTCACCGTGCTGTTTCCCTTGAGCTTGCTGGCCAGGCTGCTGTTCACCACCAACATGGCCGGATTGTGCGAGAACCTGACCATAACTATTACCGATATTGTGGCCAATTTGAAGTTTGCGAATGTGTACATGGTGAGGAAGCAGCTCCATGAGATTCGCTCTCTCCTAAGGCTCATGGACGCTAGAGCCCGGCTGGTGGGCGATCCCGAGGAGATTTCTGCCTTGAGGAAGGAAGTGAATATCGCACAGGGCACTTTCCGCACCTTTGCCAGTATTTTCGTATTTGGCACTACTTTGAGTTGCGTCCGCGTGGTCGTTCGCCCGGATCGAGAGCTCCTGTATCCGGCCTGGTTCGGCGTTGACTGGATGCACTCCACCAGAAACTATGTGCTCATCAATATCTACCAGCTCTTCGGCTTGATAGTGCAGGCTATACAGAACTGCGCTAGTGACTCCTATCCGCCTGCGTTTCTCTGCCTGCTCACGGGTCATATGCGTGCTTTGGAGCTGAGGGTGCGGCGGATTGGCTGCAGGACGGAAAAGTCCAATAAAGGGCAGACATATGAAGCCTGGCGGGAGGAGGTGTACCAGGAACTCATCGAGTGCATCCGCGATCTGGCGCGGGTCCATCGGCTGAGGGAGATCATTCAGCGGGTCCTTTCAGTGCCCTGCATGGCCCAGTTCGTCTGCTCCGCCGCCGTCCAGTGTACCGTCGCCATGCACTTCCTGTACGTAGCGGATGACCACGACCACACCGCCATGATCATCTCGATTGTATTTTTCTCGGCCGTCACCTTGGAGGTGTTTGTAATCTGCTATTTTGGGGACAGGATGCGGACACAGAGCGAGGCGCTGTGCGATGCCTTCTACGATTGCAACTGGATAGAACAGCTGCCCAAGTTCAAGCGCGAACTGCTCTTCACCCTGGCCAGGACGCAGCGGCCTTCTCTTATTTACGCAGGCAACTACATCGCACTCTCGCTGGAGACCTTCGAGCAGGTCATGAGGTTCACATACTCTGTTTTCACACTCTTGCTGAGGGCCAAGTAAGAACTTTATAATCTCTTTTTGGGGAGAAAAATTTTAAAGCACAATAGCAGAAAAATATATCAGATAATATAACAAAAAAAAAAAAAAAAAA DOR64 (SEQ ID NO: 12)MKLSETLKIDYFRVQLNAWRICGALDLSEGRYWSWSMLLCILVYLPTPMLLRGVYSFEDPVENNFSLSLTVTSLSNLMKFCMYVAQLTKMVEVQSLIGQLDARVSGESQSERHRNMTEHLLRMSKLFQITYAVVFIIAAVPFVFETELSLPMPMWFPFDWKNSMVAYIGALVFQEIGYVFQIMQCFAADSFPPLVLYLISEQCQLLILRISEIGYGYKTLEENEQDLVNCIRDQNALYRLLDVTKSLVSYPMMVQFMVIGINIAITLFVLIFYVETLYDRIYYLCFLLGITVQTYPLCYYGTMVQESFAELHYAVFCSNWVDQSASYRGHMLILAERTKRMQLLLAGNLVPIHLSTYVACWKGAYSFFTLMADRDGLGS DOR64nt (SEQ ID NO: 11)GGCACGAGCCAAGAATTCAAAATGAAACTCAGCGAAACCCTAAAAATCGACTATTTTCGAGTCCAGTTGAATGCCTGGCGAATTTGTGGTGCCTTGGATCTCAGCGAGGGTAGGTACTGGAGTTGGTCGATGCTATTGTGCATCTTGGTGTACCTGCCGACACCCATGCTACTGAGAGGAGTATACAGTTTCGAGGATCCGGTGGAAAATAATTTCAGCTTGAGCCTGACGGTCACATCGCTGTCCAATCTCATGAAGTTCTGCATGTACGTGGCCCAACTAACAAAGATGGTCGAGGTCCAGAGTCTTATTGGTCAGCTGGATGCCCGGGTTTCTGGCGAGAGCCAGTCTGAGCGTCATAGAAATATGACCGAGCACCTGCTAAGGATGTCCAAGCTGTTCCAGATCACCTACGCTGTAGTCTTCATCATTGCTGCAGTTCCCTTCGTTTTCGAAACTGAGCTAAGCTTACCCATGCCCATGTGGTTTCCCTTCGACTGGAAGAACTCGATGGTGGCCTACATCGGAGCTCTGGTTTTCCAGGAGATTGGCTATGTCTTTCAAATTATGCAATGCTTTCCAGCTGACTCGTTTCCCCCGCTCGTACTGTACCTGATCTCCGAGCAATGTCAATTGCTGATCCTGAGAATCTCTGAAATCGGATATGGTTACAAGACTCTGGAGGAGAACGAACAGGATCTGGTCAACTGCATCAGGGATCAAAACGCGCTGTATAGATTACTCGATGTGACCAAGAGTCTCGTTTCGTATCCCATGATGGTGCAGTTTATGGTTATTGGCATCAACATCGCCATCACCCTATTTGTCCTGATATTTTACGTGGAGACCTTGTACGATCGCATCTATTATCTTTGCTTTCTCTTGGGCATCACCGTGCAGACATATCCATTGTGCTACTATGGAACCATGGTGCAGGAGAGTTTTGCTGAGCTTCACTATGCGGTATTCTGCAGCAACTGGGTGGATCAAAGTGCCAGCTATCGTGGGCACATGCTCATCCTGGCGGAGCGCACTAAGCGGATGCAGCTTCTCCTCGCCGGCAACCTGGTGCCCATCCACCTGAGCACCTACGTGGCCTGTTGGAAGGGAGCCTACTCCTTCTTCACCCTGATGGCCGATCGAGATGGCCTGGGTTCTTAGTAGCCCAGTCATTTCACTCACATTCTACATCAAGTAGTACTACCACTGAACACGAACACGAATATTTCAAAAGTAAACACATAATATTCACAATAGTGTATCACTTTAATAAAATTTTTGGTTACCATGAAAAAAAAAA AAAAAAAA DOR67 (SEQID NO: 10) MLSQFFPHIKEKPLSERVKSRDAFVYLDRVMWSFGWTVPENKRWDLHYKLWSTFVTLVIFILLPISVSVEYIQRFKTFSAGEFLSSIQIGVNMYGSSFKSYLTMMGYKKRQEAKMSLDELDKRCVCDEERTIVHRHVALGNFCYIFYHIAYTSFLISNFLSFIMKRIHAWRMYFPYVDPEKQFYISSIAEVILRGWAVFMDLCTDVCPLISMVIARCHITLLKQRLRNLRSEPGRTEDEYLKELADCVRDHRLILDYVDALRSVFSGTIFVQFLLIGIVLGLSMINIMFFSTLSTGVAVVLFMSCVSMQTFPFCYLCNMIMDDCQEMADSLFQSDWTSADRRYKSTLVYFLHNLQQPIILTAGGVFPISMQTNLNMVKLAFTVVTIVKQFNLAEKFQ DOR67nt (SEQ ID NO: 9)GGCACGAGGAAATGTTAAGCCAGTTCTTTCCCCACATTAAAGAAAAGCCATTGAGCGAGCGGGTTAAGTCCCGAGATGCCTTCGTTTACTTAGATCGGGTGATGTGGTCCTTTGGCTGGACAGTGCCTGAAAACAAAAGGTGGGATCTACATTACAAACTGTGGTCAACTTTCGTGACATTGGTGATATTTATCCTTCTGCCGATATCGGTAAGCGTTGAGTATATTCAGCGGTTCAAGACCTTCTCGGCGGGTGAGTTTCTTAGCTCAATCCAGATTGGCGTTAACATGTACGGAAGCAGCTTTAAAAGTTATTTGACCATGATGGGATATAAGAAGAGACAGGAGGCTAAGATGTCACTGGATGAGCTGGACAAGAGATGCGTTTGTGATGAGGAGAGGACCATTGTACATCGACATGTCGCCCTGGGAAACTTTTGCTATATTTTCTATCACATTGCGTACACTAGCTTTTTGATTTCAAACTTTTTGTCATTTATAATGAAGAGAATCCATGCCTGGCGCATGTACTTTCCCTACGTCGACCCCGAAAAGCAATTTTACATCTCTAGCATCGCCGAAGTCATTCTTAGGGGGTGGGCCGTCTTCATGGATCTCTGCACGGATGTGTGTCCTTTGATCTCCATGGTAATAGCACGATGCCACATCACCCTTCTGAAACAGCGCCTGCGAAATCTACGATCGGAACCAGGAAGGACGGAAGATGAGTACTTGAAGGAGCTCGCCGACTGCGTTCGAGATCACCGCTTGATATTGGACTATGTCGACGCATTGCGATCCGTCTTTTCGGGGACAATTTTTGTGCAGTTCCTCTTGATCGGTATTGTACTGGGTCTGTCAATGATAAATATAATGTTTTTCTCAACACTTTCGACTGGTGTCGCCGTTGTCCTTTTTATGTCCTGCGTATCTATGCAGACGTTCCCCTTTTGCTATTTGTGTAACATGATTATGGATGACTGCCAAGAGATGGCCGACTCCCTTTTTCAATCGGACTGGACATCTGCCGATCGTCGCTACAAATCCACTTTGGTATACTTTCTTCACAATCTTCAGCAGCCCATTATTCTTACGGCTGGTGGAGTCTTTCCTATTTCCATGCAAACAAATTTAAATATGGTGAAGCTGGCCTTTACTGTGGTTACAATAGTGAAACAATTTAACTTGGCAGAAAAGTTTCAATAAGTTAAGATATGCAAGCTCTGCTATTATAAACCTACACTCGAGAAAATATTTCTTCACATTAATAAACCTTCAGTACTTACTGCTTGTGGCGCCCC CGGAAAAAAAAAAAAAAAAAADOR68 (SEQ ID NO: 82) MSKLIEVFLGNLWTQRFTFARMGLDLQPDKKGNVLRSPLLYCIMCLTTSFELCTVCAFMVQNRNQIVLCSEALMHGLQMVSSLLKMAIFLAKSHDLVDLIQQIQSPFTEEDLVGTEWRSQNQRGQLMAAIYFMMCAGTSVSFLLMPVALTMLKYHSTGEFAPVSSFRVLLPYDVTQPHVYAMDCCLMVFVLSFFCCSTTGVDTLYGWCALGVSLQYRRLGQQLKRIPSCFNPSRSDFGLSGIFVEHARLLKIVQHFNYSFMEIAFVEVVIICGLYCSVICQYIMPHTNQNFAFLGFFSLVVTTQLCIYLFGAEQVRLEAERFSRLLYEVIPWQNLPPKHRKLFLFPIERAQRETVLGAYFFELGRPLLVWVSIFLFIVLLF DOR68nt (SEQ ID NO: 81)ATGTCAAAGCTAATCGAGGTGTTTCTGGGTAATCTGTGGACCCAGCGTTTTACCTTCGCCCGAATGGGTTTGGATTTGCAGCCCGATAAAAAGGGCAATGTTTTGCGATCTCCGCTTCTTTATTGTATTATGTGTCTGACAACAAGCTTTGAGCTCTGCACCGTGTGCGCCTTTATGGTCCAAAATCGCAACCAAATCGTGCTTTGTTCCGAGGCCCTGATGCACGGACTACAGATGGTCTCCTCGCTACTGAAGATGGCTATATTCTTGGCCAAATCTCACGACCTGGTGGACCTAATTCAACAGATTCAGTCGCCTTTTACAGAGGAGGATCTTGTAGGTACAGAGTGGAGATCCCAAAATCAAAGGGGACAACTAATGGCTGCCATTTACTTTATGATGTGTGCCGGTACGAGTGTGTCATTTCTGTTGATGCCAGTGGCTTTGACCATGCTTAAGTACCATTCCACTGGGGAATTCGCGCCTGTCAGCTCGTTCCGGGTTCTGCTTCCATACGATGTGACACAACCGCATGTTTATGCCATGGACTGCTGCTTGATGGTATTTGTGTTAAGTTTTTTTTGCTGCTCCACCACCGGAGTGGATACCTTATATGGATGGTGTGCTTTAGGCGTGAGTTTACAATACCGTCGCCTCGGTCAACAACTTAAAAGGATACCCTCCTGTTTCAATCCATCTCGGTCTGACTTTGGATTAAGTGGGATTTTTGTGGAGCATGCTCGTCTGCTTAAAATAGTCCAACATTTTAATTATAGTTTTATGGAGATCGCATTTGTGGAGGTTGTTATAATCTGTGGACTCTATTGCTCAGTAATTTGTCAGTATATAATGCCACACACCAACCAAAACTTCGCCTTTCTGGGTTTCTTTTCATTGGTAGTTACCACACAGCTGTGCATCTATCTTTTCGGTGCCGAACAGGTCCGTTTGGAGGCTGAGCGATTTTCCCGGCTGCTATACGAAGTAATTCCTTGGCAAAACCTTCCTCCTAAACACCGGAAACTTTTCCTTTTTCCAATTGAGCGCGCCCAACGAGAAACTGTTCTCGGTGCTTATTTCTTCGAACTAGGCAGACCTCTTCTTGTTTGGGTAAGCATATTCCTTTTTATTGTATTATTATTT DOR71g (SEQ ID NO: 14)MVIIDSLSFYRPFWICMRLLVPTFFKDSSRPVQLYVVLLHILVTLWFPLHLLLHLLLLPSTAEFFKNLTMSLTCVACSLKHVAHLYHLPQIVEIESLIEQLDTFIASEQEHRYYRDHVHCHARRFTRCLYISFGMIYALFLFGVFVQVISGNWELLYPAYFPFDLESNRFLGAVALGYQVFSMLVEGFQGLGNDTYTPLTLCLLAGHVHLWSIRMGQLGYFDDETVVNHQRLLDYIEQHKLLVRFHNLVSRTISEVQLVQLGGCGATLCIIVSYMLFFVGDTISLVYYLVFFGVVCVQLFPSCYFASEVAEELERLPYAIFSSRWYDQSRDHRFDLLIFTQLTLGNRGWIIKAGGLIELNLNAFFATLKMAYSLFAVVHRETGNPLQREH DOR71gnt (SEQ ID NO: 13)ATGGTCATTATCGACAGTCTTAGTTTTTATCGTCCATTCTGGATCTGCATGCGATTGCTGGTACCGACTTTCTTCAAGGATTCCTCACGTCCTGTCCAGCTGTACGTGGTGTTGCTGCACATCCTGGTCACCTTGTGGTTTCCACTGCATCTGCTGCTGCATCTTCTGCTACTTCCATCTACCGCTGAGTTCTTTAAGAACCTGACCATGTCTCTGACTTGTGTGGCCTGCAGTCTGAAGCATGTGGCCCACTTGTATCACTTGCCGCAGATTGTGGAAATCGAATCACTGATCGAGCAATTAGACACATTTATTGCCAGCGAACAGGAGCATCGTTACTATCGGGATCACGTACATTGCCATGCTAGGCGCTTTACAAGATGTCTCTATATTAGCTTTGGCATGATCTATGCGCTTTTCCTGTTCGGCGTCTTCGTTCAGGTTATTAGCGGAAATTGGGAACTTCTCTATCCAGCCTATTTCCCATTCGACTTGGAGAGCAATCGCTTTCTCGGCGCAGTAGCCTTGGGCTATCAGGTATTCAGCATGTTAGTTGAAGGCTTCCAGGGGCTGGGCAACGATACCTATACCCCACTGACCCTATGCCTTCTGGCCGGACATGTCCATTTGTGGTCCATACGAATGGGTCAACTGGGATACTTCGATGACGAGACGGTGGTGAATCATCAGCGTTTGCTGGATTACATTGAGCAGCATAAACTCTTGGTGCGGTTCCACAACCTGGTGAGCCGGACCATCAGCGAAGTGCAACTGGTGCAGCTGGGCGGATGTGGAGCCACTCTGTGCATCATTGTCTCCTACATGCTCTTCTTTGTGGGCGACACAATCTCGCTGGTCTACTACTTGGTGTTCTTTGGAGTGGTCTGCGTGCAGCTCTTTCCCAGCTGCTATTTTGCCAGCGAAGTAGCCGAGGAGTTGGAACGGCTGCCATATGCGATCTTCTCCAGCAGATGGTACGATCAATCGCGGGATCATCGATTCGATTTGCTCATCTTTACACAATTAACACTGGGAAACCGGGGGTGGATCATCAAGGCAGGAGGTCTTATCGAGCTGAATTTGAATGCCTTTTTCGCCACCCTGAAGATGGCCTATTCCCTTTTTGCAGTTGTGGTGCGGGCAAAGGGTA TA DOR72g (SEQ ID NO:16) MDLKPRVIRSEDIYRTYWLYWHLLGLESNFFLNRLLDLVITIFVTIWYPIHLILGLFMERSLGDVCKGLPITAACFFASFKFICFRFKLSEIKEIEILFKELDQRALSREECEFFNQNTRREANFIWKSFIVAYGLSNISAIASVLFGGGHKLLYPAWFPYDVQATELIFWLSVTYQIAGVSLAILQNLANDSYPPMTFCVVAGHVRLLAMRLSRIGQGPEETIYLTGKQLIESIEDHRKLMKIVELLRSTMNISQLGQFISSGVNISITLVNILFFADNNFAITYYGVYFLSMVLELFPCCYYGTLISVEMNQLTYAIYSSNWMSMNRSYSRILLIFMQLTLAEVQIKAGGMIGIGMNAFFATVRLAYSFFTLAMSLR DOR72gnt (SEQ ID NO: 15)ATGGACTTAAAACCGCGAGTCATTCGAAGTGAAGATATCTACAGAACCTATTGGTTATATTGGCATCTTTTGGGCCTGGAAAGCAATTTCTTTCTGAATCGCTTGTTGGATTTGGTGATTACAATTTTCGTAACCATTTGGTATCCAATTCACCTGATTCTGGGACTGTTTATGGAAAGATCTTTGGGGGATGTCTGCAAGGGTCTACCAATTACGGCAGCATGCTTTTTCGCCAGCTTTAAATTTATTTGTTTTCGCTTCAAGCTATCTGAAATTAAAGAAATCGAAATATTATTTAAAGAGCTGGATCAGCGAGCTTTAAGTCGAGAGGAATGCGAGTTTTTCAATCAAAATACGAGACGTGAGGCGAATTTCATTTGGAAAAGTTTCATTGTGGCCTATGGACTGTCGAATATCTCGGCTATTGCATCAGTTCTTTTCGGCGGTGGACATAAGCTATTATATCCCGCCTGGTTTCCATACGATGTGCAGGCCACGGAACTAATATTTTGGCTAAGTGTAACATACCAAATTGCCGGAGTAAGTTTGGCCATACTTCAGAATTTGGCCAATGATTCCTATCCACCGATGACATTTTGCGTGGTTGCCGGTCATGTAAGACTTTTGGCGATGCGCTTGAGTAGAATTGGCCAAGGTCCAGAGGAAACAATATACTTAACCGGAAAGCAATTAATCGAAAGCATCGAGGATCACCGAAAACTAATGAAGATAGTGGAATTACTGCGCAGCACCATGAATATTTCGCAGCTCGGCCAGTTTATTTCAAGTGGTGTTAATATTTCCATAACACTAGTCAACATTCTCTTCTTTGCGGATAATAATTTCGCTATAACCTACTACGGAGTGTACTTCCTATCGATGGTGTTGGAATTATTCCCGTGCTGCTATTACGGCACCCTGATATCCGTGGAGATGAACCAGCTGACCTATGCGATTTACTCAAGTAACTGGATGAGTATGAATCGGAGCTACAGCCGCATCCTACTGATCTTCATGCAACTCACCCTGGCGGAAGTGCAGATCAAGGCCGGTGGGATGATTGGCATCGGAATGAACGCCTTCTTTGCCACCGTGCGATTGGCCTACTCCTTCTTCACTTTGGCCATGTCGCTGCGT DOR73g (SEQ ID NO: 18)MDSRRKVRSENLYKTYWLYWRLLGVEGDYPFRRLVDFTITSFITILFPVHLILGMYKKPQIQVFRSLHFTSECLFCSYKFFCFRWKLKEIKTIEGLLQDLDSRVESEEERNYFNQNPSRVARMLSKSYLVAAISAIITATVAGLFSTGRNLMYLGWFPYDFQATAAIYWISFSYQAIGSSLLILENLANDSYPPITFCVVSGHVRLLIMRLSRIGHDVKLSSSENTRKLIEGIQDHRKLMKIIRLLRSTLHLSQLGQFLSSGINISITLINILFFAENNFAMLYYAVFFAAMLIELFPSCYYGILMTMEFDKLPYAIFSSNWLKMDKRYNRSLIILMQLTLVPVNIKAGGIVGIDMSAFFATVRMAYSFYTLALSFRV DOR73gnt (SEQ ID NO: 17)ATGGATTCAAGAAGGAAAGTCCGAAGTGAAAATCTTTACAAAACCTATTGGCTTTACTGGCGACTTCTGGGAGTCGAGGGCGATTATCCTTTTCGACGGCTAGTGGATTTTACAATCACGTCTTTCATTACGATTTTATTTCCCGTGCATCTTATACTGGGAATGTATAAAAAGCCCCAGATTCAAGTCTTCAGGAGTCTGCATTTCACATCGGAATGCCTTTTCTGCAGCTATAAGTTTTTCTGTTTTCGTTGGAAACTTAAAGAAATAAAGACCATCGAAGGATTGCTCCAGGATCTCGATAGTCGAGTTGAAAGTGAAGAAGAACGCAACTACTTTAATCAAAATCCAAGTCGTGTGGCTCGAATGCTTTCGAAAAGTTACTTGGTAGCTGCTATATCGGCCATAATCACTGCAACTGTAGCTGGTTTATTTAGTACTGGTCGAAATTTAATGTATCTGGGTTGGTTTCCCTACGATTTTCAAGCAACCGCCGCAATCTATTGGATTAGTTTTTCCTATCAGGCGATTGGCTCTAGTCTGTTGATTCTGGAAAATCTGGCCAACGATTCATATCCGCCGATTACATTTTGTGTGGTCTCTGGACATGTGAGACTATTGATAATGCGTTTAAGTCGAATTGGTCACGATGTAAAATTATCAAGTTCGGAAAATACCAGAAAACTCATCGAAGGTATCCAGGATCACAGGAAACTAATGAAGATAATACGCCTACTTCGCAGCACTTTACATCTTAGCCAACTGGGCCAGTTCCTTTCTAGTGGAATCAACATTTCCATAACACTCATCAACATCCTGTTCTTTGCGGAAAACAACTTTGCAATGCTTTATTATGCGGTGTTCTTTGCTGCAATGTTAATAGAACTATTTCCAAGTTGTTACTATGGAATTCTGATGACAATGGAGTTTGATAAGCTACCATATGCCATCTTCTCCAGCAACTGGCTTAAAATGGATAAAAGATACAATCGATCCTTGATAATTCTGATGCAACTAACACTGGTTCCAGTGAATATAAAAGCAGGTGGTATTGTTGGCATCGATATGAGTGCATTTTTTGCCACAGTTCGGATGGCATATTCCTTTTACACTTTAGCCTTGTCATTTCGAGTA DOR77 (SEQ ID NO: 84)MELMRVPVQFYRTIGEDIYAHRSTNPLKSLLFKIYLYAGFINFNLLVTGELVFFYNSIQDFETIRLAIAVAPCIGFSLVADFKQAAMIRGKKTLIMLLDDLENMHPKTLAKQMEYKLPDFEKTMKRVINIFTFLCLAYTTTFSFYPAIKASVKFNFLGYDTFDRNFGFLIWFPFDATRNNLIYWIMYWDIAHGAYLAAFQVTESTVEVIIIYCIFLMTSMVQVFMVCYYGDTLIAASLKVGDAAYNQKWFQCSKSYCTMLKLLIMRSQKPASIRPPTFPPISLVTYMKNPFNNLPKHSSS LQINANRYI DOR77nt(SEQ ID NO: 83) ATGGAATTGATGCGAGTGCCAGTACAGTTTTACAGAACGATTGGAGAGGATATCTACGCCCATCGATCCACGAATCCCCTAAAATCGCTTCTCTTCAAGATCTATCTATATGCGGGATTCATAAATTTTAATCTGTTGGTAATCGGTGAACTGGTGTTCTTCTACAACTCAATTCAGGACTTTGAAACCATTCGATTGGCCATCGCGGTGGCTCCATGTATCGGATTTTCTCTGGTTGCTGATTTTAAACAAGCTGCCATGATTAGAGGCAAGAAAACACTAATTATGCTACTCGATGATTTGGAGAACATGCATCCGAAAACCCTGGCAAAGCAAATGGAATACAAATTGCCGGACTTTGAAAAGACCATGAAACGTGTGATCAATATATTCACCTTTCTCTGCTTGGCCTATACGACTACGTTCTCCTTTTATCCGGCCATCAAGGCATCCGTGAAATTTAATTTCTTGGGCTACGACACCTTTGATCGAAATTTTGGTTTCCTCATCTGGTTTCCCTTCGATGCAACAAGGAATAATTTGATATACTGGATCATGTACTGGGACATAGCCCATGGGGCCTATCTAGCGGCCTTTCAGGTCACCGAATCAACAGTGGAAGTGATTATTATTTACTGCATTTTTTTGATGACCTCGATGGTTCAGGTATTTATGGTGTGCTACTATGGGGATACTTTAATTGCCGCGAGCTTGAAAGTGGGCGATGCCGCTTACAACCAAAAGTGGTTTCAGTGCAGCAAATCCTATTGCACCATGTTGAAGTTGCTAATCATGAGGAGTCAGAAACCAGCTTCAATAAGACCGCCGACTTTTCCCCCCATATCCTTGGTTACCTATATGAAGAATCCCTTCAACAATCTACCCAAACACAGCTCTTCCCTGCAAATCAACGCCAATCGCTATATC DOR78 (SEQ ID NO: 86)MKFMKYAVFFYTSVGIEPYTIDSRSKKASLWSRLLFWANVINLSVIVFGEILYLGVAYSDGKFIDAVTVLSYIGFVIVGMSKMFFIWWKKTDLSDLVKELEHIYPNGKAEEEMYRLDRYLRSCSRISITYALLYSVLIWTFNLFSIMQFLVYEKLLKIRVVGQTLPYLMYFPWNWHENWTYYVLLFCQNFAGHTSASGQISTDLLLCAVATQVVMHFDYLARVVEKQVLDRDWSENSRFLAKTVQYHQRILRLMDVLNDIFGIPLLLNFMVSTFVICFVGFQMTVGVPPDIMIKLFLFLFSSLSQVYLICHYGQLIADAVRDFRSSSLSISAYKQNWQNADIRYRRALVFFIARPQRTTYLKATIFMNITRATMTDVRYNLKCH DOR78nt (SEQ ID NO: 85)ATGAAGTTCATGAAGTACGCAGTTTTCTTTTACACATCGGTGGGCATTGAGCCGTATACGATTGACTCGCGGTCCAAAAAAGCGAGCCTATGGTCACATCTTCTCTTCTGGGCCAATGTGATCAATTTAAGTGTCATTGTTTTCGGAGAGATCCTCTATCTGGGAGTGGCCTATTCCGATGGAAAGTTCATTGATGCCGTCACTGTACTGTCATATATCGGATTCGTAATCGTGGGCATGAGCAAGATGTTCTTCATATGGTGGAAGAAGACCGATCTAAGCGATTTGGTTAAGGAATTGGAGCACATCTATCCAAATGGCAAAGCTGAGGAGGAGATGTATCGGTTGGATAGGTATCTGCGATCTTGTTCACGAATTAGCATTACCTATGCACTACTCTACTCCGTACTCATCTGGACCTTCAATCTGTTCAGTATCATGCAATTCCTTGTCTATGAAAAGTTGCTTAAAATCCGAGTGGTCGGCCAAACGCTGCCATATTTGATGTACTTTCCCTGGAACTGGCATGAAAACTGGACGTATTATGTGCTGCTGTTCTGTCAAAACTTCGCAGGACATACTTCGGCATCGGGACAGATCTCTACGGATCTTTTGCTTTGTGCTGTTGCTACCCAGGTGGTAATGCACTTCGATTACTTGGCCAGAGTGGTGGAAAAACAAGTGTTAGATCGCGATTGGAGCGAAAACTCCAGATTTTTGGCAAAAACTGTACAATATCATCAGCGCATTCTTCGGCTAATGGACGTTCTCAACGATATATTCGGGATACCGCTACTGCTTAACTTTATGGTCTCCACATTTGTCATCTGCTTTGTGGGATTCCAAATGACCGTGGGTGTCCCGCCGGACATCATGATTAAGCTCTTCTTGTTCCTGTTCTCGTCCTTGTCGCAAGTGTACTTGATATGCCACTACGGCCAGCTGATTGCCGATGCGGTAAGAGACTTTCGAAGCTCTAGCTTATCGATTTCTGCATATAAGCAGAATTGGCAAAATGCTGACATTCGCTATCGTCGGGCTCTGGTATTCTTTATAGCTCGACCTCAGAGGACAACTTATCTAAAAGCTACAATTTTCATGAATATAACAAGGGCCACCATGACGGACGTAAGATACAATTTGAAATGTC AT DOR81 (SEQ ID NO:88) MMETLRNSGLNLKNDFGIGRKIWRVFSFTYNMVILPVSFPINYVIHLAEFPPELLLQSLQLCLNTWCFALKFFTLIVYTHRLELANKHFDELDKYCVKPAEKRKVRDMVATITRLYLTFVVVYVLYATSTLLDGLLHHRVPYNTYYPFINWRVDRTQMYIQSFLEYFTVGYAIYVATATDSYPVIYVAALRTHILLLKDRIIYLGDPSNEGSSDPSYMFKSLVDCIKAHRTMLNFCDAIQPIISGTIFAQFIICGSILGIIMINMVLFADQSTRFGIVIYVMAVLLQTFPLCFYCNAIVDDCKELAHALFHSAWWVQDKRYQRTVIQFLQKLQQPMTFTAMNIFNINLATNINVSPLLSVRTGKEAKSELQSLQVAKFAFTVYAIASGMNLDQKLSIKE DOR81nt (SEQ ID NO:87) ATGATGGAGACGCTGCGAAATTCGGGCTTGAATTTGAAGAACGATTTCGGTATAGGCCGCAAGATTTGGAGGGTGTTTTCGTTCACCTACAATATGGTGATACTTCCCGTAAGTTTCCCAATCAACTATGTGATACATCTGGCGGAGTTCCCGCCGGAGCTGCTGCTGCAATCCCTGCAACTGTGCCTCAACACTTGGTGCTTCGCTCTGAAGTTCTTCACTCTGATCGTCTATACGCACCGCTTGGAGCTGGCCAACAAGCACTTTGACGAATTGGATAAGTACTGCGTGAAGCCGGCGGAGAAGCGCAAGGTTCGCGACATGGTGGCCACTATTACAAGACTGTACCTGACCTTCGTCGTGGTCTACGTCCTCTACGCCACCTCCACGCTACTGGACGGACTACTGCACCACCGTGTTCCCTACAATACGTACTATCCGTTCATAAACTGGCGAGTCGATCGGACCCAGATGTACATCCAGAGTTTTCTGGAGTACTTCACCGTGGGTTATGCCATATATGTGGCCACCGCCACCGATTCCTACCCTGTGATTTACGTGGCAGCCCTGCGAACTCATATTCTCTTGCTCAAGGACCGTATCATTTACTTGGGCGATCCCAGCAACGAGGGTAGCAGCGACCCGAGCTACATGTTTAAATCGTTGGTGGATTGTATCAAGGCACACAGAACCATGCTAAAGTGCAGTTTTTGTGATGCCATTCAACCAATCATCTCTGGCACGATATTTGCCCAATTCATCATATGCGGATCGATCCTGGGCATAATTATGATCAACATGGTATTGTTCGCTGATCAATCGACCCGATTCGGCATACTCATCTACGTTATGGCCGTCCTTCTGCAGACTTTTCCGCTTTGCTTCTACTGCAACGCCATCGTGGACGACTGCAAAGAACTGGCCCACGCACTTTTCCATTCCGCCTGGTGGGTGCAGGACAAGCGATACCAGCGGACTGTCATCCAGTTCCTGCAGAAACTGCAGCAGCCCATGACCTTCACCGCCATGAACATATTTAACATTAATTTGGCCACTAACATCAATGTAAGTCCACTGCTCTCGGTTAGAACGGGGAAGGAAGCAAAGTCCGAACTTCAATCCTTGCAGGTAGCCAAGTTCGCCTTCACCGTGTACGCCATCGCGAGCGGTATGAACCTGGACCAAAAGTTAAGCATTAAG GAA DOR82 (SEQ ID NO:90) MACIPRYQWKGRPTERQFYASEQRIVFLLGTICQIFQITGVLIYWYCNGRLATETGTFVAQLSEMCSSFCLTFVGFCNVYAISTNRNQIETLLEELHQIYPRYRKNHYRCQHYFDMAMTIMRIEFLFYMILYVYYNSAPLWVLLWEHLHEEYDLSFKTQTNTWFPWKVHGSALGFGMAVLSITVGSFVGVGFSIVTQNLICLLTFQLKLHYDGISSQLVSLDCRRPGAHKELSILIAHHSRILQLGDQVNDIMNFVFGSSLVGATIAICMSSVSIMLLDLASAFKYASGLVAFVLYNFVICYMGTEVTLAVKIGSYMDGRRWIPKDSLLRSQRLQVLVAVGFFNICVLSNRRPKIEILLRYYYHIMFYSFKLYFSLRKGSLWKILSSFTLLRI DOR82nt (SEQ ID NO: 89)ATGGCATGCATACCAAGATATCAATGGAAAGGACGCCCTACTGAAAGACAGTTCTACGCTTCGGAGCAAAGGATAGTGTTCCTTCTTGGAACCATTTGCCAGATATTCCAGATTACTGGAGTGCTTATCTATTGGTATTGCAATGGCCGTCTTGCCACGGAAACGGGCACCTTTGTGGCACAATTATCTGAAATGTGCAGTTCTTTTTGTCTAACATTTGTGGGATTCTGTAACGTTTATGCGATCTCTACAAACCGCAATCAAATTGAAACATTACTCGAGGAGCTTCATCAGATATATCCGAGATACAGGAAAAATCACTATCGCTGCCAGCATTATTTTGACATGGCCATGACAATAATGAGAATTGAGTTTCTTTTCTATATGATCTTGTACGTGTACTACAATAGTGCACCATTATGGGTGCTTCTTTGGGAACACTTGCACGAGGAATATGATCTTAGCTTCAAGACGCAGACCAACACTTGGTTTCCATGGAAAGTCCATGGGTCGGCACTTGGATTTGGTATGGCTGTACTAAGCATAACCGTGGGATCCTTTGTGGGCGTAGGTTTCAGTATTGTCACCCAGAATCTTATCTGTTTGTTAACCTTCCAACTAAAGTTGCACTACGATGGAATATCCAGTCAGTTAGTATCTCTCGATTGCCGTCGTCCTGGAGCTCATAAGGAGTTGAGCATCCTCATCGCCCACCACAGCCGAATCCTTCAGCTGGGCGACCAAGTCAATGACATAATGAACTTTGTATTCGGCTCTAGCCTAGTAGGTGCCACTATTGCCATTTGTATGTCAAGTGTTTCTATAATGCTACTGGACTTAGCATCTGCCTTCAAATATGCCAGTGGTCTAGTGGCATTCGTCCTCTACAACTTTGTCATCTGCTACATGGGAACCGAGGTCACTTTAGCTGTGAAGATTCGTTCATATATGGACGGAAGGCGGTGGATACCCAAAGATTCGTTGCTGAGATCTCAGAGGCTACAGGTGCTCGTCGCAGTTGGATTTTTTAATATATGTGTCCTCTCGAATCGTCGTCCTAAAATTGAAATTTTGCTTAGATATTATTACCATATTATGTTTTATTCATTTAAATTATATTTTTCTTTAAGGAAAGGTAGCCTTTGGAAAATCTTGTCTTCTTTCACCTTATTGAGGATC DOR83 (SEQ ID NO: 92)MQLEDFMRYPDLVCQAAQLPRYTWNGRRSLEVKRNLAKRIIFWLGAVNLVYHNIGCVMYGYFGDGRTKDPIAYLAELASVASMLGFTIVGTLNLWKMLSLKTHFENLLNEFEELFQLIKHRAYRIHHYQEKYTRHIRNTFIFHTSAVVYYNSLPILLMIREHFSNSQQLGYRIQSNTWYPWQVQGSIPGFFAAVACQIFSCQTNMCVNMFIQFLINFFGIQLEIHFDGLARQLETIDARNPHAKDQLKYLIVYHTKLLNLADRVNRSFNFTFLISLSVSMISNCFLAFSMTMFDFGTSLKHLLGLLLFITYNFSMCRSGTHLILTSGKVLPAAFYNNWYEGDLVYRRMLLILMMRATKPYMWKTYKLAPVSITTYMAECKTKEAHEQRHFRRHERQKPRV ARI DOR83nt (SEQ IDNO: 91) ATGCAGTTGGAGGACTTTATGCGGTACCCGGACCTCGTGTGTCAAGCGGCCCAACTTCCCAGATACACGTGGAATGGCAGACGATCCTTGGAAGTTAAACGCAACTTGGCAAAACGCATTATCTTCTGGCTTGGAGCAGTAAATTTGGTTTATCACAATATTGGCTGCGTCATGTATGGCTATTTCGGTGATGGAAGAACAAAGGATCCAATTGCGTATTTAGCTGAATTGGCATCTGTGGCCAGCATGCTTGGTTTCACCATTGTGGGCACCCTCAACTTGTGGAAGATGCTGAGCCTTAAGACCCATTTTGAGAACCTACTAAATGAATTCGAGGAATTATTTCAACTAATCAAGCACAGGGCGTATCGCATACACCACTATCAAGAAAAGTATACGCGTCATATACGAAATACATTTATTTTCCATACCTCTGCCGTTGTCTACTACAACTCACTACCAATTCTTCTAATGATTCGGGAACATTTCTCGAACTCACAGCAGTTGGGCTATAGAATTCAGAGTAATACCTGGTATCCCTGGCAGGTTCAGGGATCAATTCCTGGATTTTTTGCTGCAGTCGCCTGTCAAATCTTTTCGTGCCAAACCAATATGTGCGTCAATATGTTTATCCAGTTTCTGATCAACTTTTTTGGTATCCAGCTAGAAATACACTTCGATGGTTTGGCCAGGCAGCTGGAGACCATCGATGCCCGCAATCCCCATGCCAAGGATCAATTGAAGTATCTGATTGTATATCACACAAAATTGCTTAATCTAGCCGACAGAGTTAATCGATCGTTTAACTTTACGTTTCTCATAAGTCTGTCGGTATCCATGATATCCAACTGTTTTCTGGCATTTTCCATGACCATGTTCGACTTTGGCACCTCTCTAAAACATTTACTCGGACTTTTGCTATTCATCACATATAATTTTTCAATGTGCCGCAGTGGTACGCACTTGATTTTAACGAGTGGCAAAGTATTGCCAGCGGCCTTTTATAACAATTGGTATGAAGGCGATCTTGTTTATCGAAGGATGCTCCTCATCCTGATGATGCGTGCTACGAAACCTTATATGTGGAAAACCTACAAGCTGGCACCTGTATCCATAACTACATATATGGCAGAATGCAAAACAAAAGAAGCCCATGAACAACGCCATTTTAGACGCCATGAAAGACAAAAACCTCGGGTT GCACGAATA DOR84 (SEQID NO: 94) MVFSFYAEVATLVDRLRDNENFLESCILLSYVSFVVMGLSKIGAVMKKKPKMTALVRQLETCFPSPSAKVQEEYAVKSWLKRCHIYTKGFGGLFMIMYFAHALIPLFIYFIQRVLLHYPDAKQIMPFYQLEPWEFRDSWLFYPSYFHQSSAGYTATCGSIAGDLMIFAVVLQVIMHYERLAKVLREFKIQAHNAPNGAKEDIRKLQSLVANHIDILRLTDLMNEVFGIPLLLNFIASALLVCLVGVQLTIALSPEYFCKQMLFLISVLLEVYLLCSFSQRLIDAVC DOR84nt (SEQ ID NO: 93)ATGGTGTTTAGTTTTTATGCCGAGGTAGCGACTCTGGTGGACAGGTTACGCGATAATGAAAATTTTCTCGAGAGCTGCATCTTACTGAGCTACGTGTCCTTTGTGGTCATGGGCCTCTCCAAGATAGGTGCTGTAATGAAAAAAAAGCCAAAAATGACAGCTTTGGTCAGGCAATTGGAGACCTGCTTTCCGTCGCCAAGTGCAAAGGTTCAAGAGGAATATGCTGTGAAGTCCTGGCTGAAACGCTGCCATATATACACAAAGGGATTTGGTGGTCTCTTCATGATCATGTATTTCGCTCACGCTCTGATTCCCTTATTCATATACTTCATTCAAAGAGTGCTGCTCCACTATCCGGATGCCAAGCAGATTATGCCGTTTTACCAACTCGAACCTTGGGAATTTCGCGACTCCTGGTTGTTTTATCCAAGCTATTTTCACCAGTCGTCGGCCGGATATACGGCTACATGTGGATCCATTGCCGGTGACCTAATGATCTTCGCTGTGGTCCTGCAGGTCATCATGCACTACGAAAGACTGGCCAAGGTTCTTAGGGAGTTTAAGATTCAAGCCCATAACGCACCCAATGGAGCTAAGGAGGATATAAGGAAGTTGCAGTCCCTAGTCGCCAATCACATTGATATACTTCGACTCACTGATCTGATGAACGAGGTCTTTGGAATTCCCTTGTTGCTAAACTTTATTGCATCTGCGCTGCTGGTCTGCCTGGTGGGAGTTCAATTAACCATCGCTTTAAGTCCAGAGTATTTTTGCAAGCAGATGCTATTTCTGATTTCCGTACTGCTTGAGGTCTATCTCCTTTGCTCCTTCAGCCAGAGGTTAATAGATG CTGTATGT DOR87 (SEQID NO: 6) MTIEDIGLVGINVRNWRHLAVLYPTPGSSWRKFAFVLPVTAMNLMQFVYLLRMWGDLPAFILNMFFFSAIFNALMRTWLVIIKRRQFEEFLGQLATLFHSILDSTDEWGRGILRRAEREARNLAILNLSASFLDIVGALVSPLFREERAHPFGVALPGVSMTSSPVYEVIYLAQLPTPLLLSMMYMPFVSLFAGLAIFGKAMLQILVHRLGQIGGEEQSEEERFQRLASCIAYHTQVMRYVWQLNKLVANIVAVEAIIFGSIICSLLFCLNIITSPTQVISIVMYILTMLYVLFTYYNRANEICLENNRVAEAVYNVPWYEAGTRFRKTLLIFLMQTQHPMEIRVGNVYPMTLAMFQSLLNASYSYFTMLRGVTGK DOR87nt (SEQ ID NO: 5)GGCACGAGGCTTATAGAAAGTGCCGAGCAATGACAATCGAGGATATCGGCCTGGTGGGCATCAACGTGCGGATGTGGCGACACTTGGCCGTGCTGTACCCCACTCCGGGCTCCAGCTGGCGCAAGTTCGCCTTCGTGCTGCCGGTGACTGCGATGAATCTGATGCAGTTCGTCTACCTGCTGCGGATGTGGGGCGACCTGCCCGCCTTCATTCTGAACATGTTCTTCTTCTCGGCCATTTTCAACGCCCTGATGCGCACGTGGCTGGTCATAATCAAGCGGCGCCAGTTCGAGGAGTTTCTCGGCCAACTGGCCACTCTGTTCCATTCGATTCTCGACTCCACCGACGAGTGGGGGCGTGGCATCCTGCGGAGGGCGGAACGGGAGGCTCGGAACCTGGCCATCCTTAATTTGAGTGCCTCCTTCCTGGACATTGTCGGTGCTCTGGTATCGCCGCTTTTCAGGGAGGAGAGAGCTCATCCCTTCGGCGTAGCTCTACCAGGAGTGAGCATGACCAGTTCACCCGTCTACGAGGTTATCTACTTGCCCCAACTGCCTACGCCCCTGCTGCTGTCCATGATGTACATGCCTTTCGTCAGCCTTTTTGCCGGCCTGGCCATCTTTGGGAAGGCCATGCTGCAGATCCTGGTACACAGGCTGGGCCAGATTGGCGGAGAAGAGCAGTCGGAGGAGGAGCGCTTCCAAAGGCTGGCCTCCTGCATTGCGTACCACACGCAGGTGATGCGCTATGTGTGGCAGCTCAACAAACTGGTGGCCAACATTGTGGCGGTGGAAGCAATTATTTTTGGCTCGATAATCTGCTCACTGCTCTTCTGTCTGAATATTATAACCTCACCCACCCAGGTGATCTCGATAGTGATGTACATTCTGACCATGCTGTACGTTCTCTTCACCTACTACAATCGGGCCAATGAAATATGCCTCGAGAACAACCGGGTGGCGGAGGCTGTTTACAATGTGCCCTGGTACGAGGCAGGAACTCGGTTTCGCAAAACCCTCCTGATCTTCTTGATGCAAACACAACACCCGATGGAGATAAGAGTCGGCAACGTTTACCCCATGACATTGGCCATGTTCCAGAGTCTGTTGAATGCGTCCTACTCCTACTTTACCATGCTGCGTGGCGTCACCGGCAAATGAGCTGAAAGACCGAAAAAACCGGAGTATCCCCTTCCATATTCCCCCTGCTCCTTTATTTTCCTTTCCTTTTCCCTTTCCGTTTTCCCATTCGCTTTTCCAGCAATCCGGGTAATGCAAAAAGTTGTTGCTGGCTGTGGTCCTGGCTGCTTGTTTGGCATTTGCATATGCTTGTCGTTTGAAAGGATTTAATCGGACTGCTGGCACGGAGTCGGCATCCTGGCTCCTGGATCCTGGCATGCAAATAGTTGGCTTCTTAGATTGTTACACAAAATAGATTGTAGATTGCAGCTGAATGTTGTGCTTGGAATAAAGTCAAAAGGATGTGGAGTCGGCCCAAGGCTCTGCCCATTCTGTTTGCTCGGGATGCCCGAAAGTATGAAAAAAAAAAAA AAAAAA DOR91 (SEQ IDNO: 96) MVRYVPRFADGQKVKLAWPLAVFRLNHIFWPLDPSTGKWGRYLDKVLAVAMSLVFMQHNDAELRYLRFEASNRNLDAFLTGMPTYLILVEAQFRSLHILLHFEKLQKFLEIFYANIYIDPRKEPEMFRKVDGKMIINRLVSAMYGAVISLYLIAPVFSIINQSKDFLYSMIFPFDSDPLYIFVPLLLTNVWVGIVIDTMMFGETNLLCELIVHLNGSYMLLKRDLQLAIEKILVARDRPHMAKQLKVLITKTLRKNVALNQFGQQLEAQYTVRVFIMFAFAAGLLCALSFKAYTTDSLSTMYYLTHWEQILQYSTNPSENLRLLKLINLAIEMNSKPFYVTGLKYFRVSLQAGLKRQKFLRSASSSTLSTADVLAFAFAFTRWLL DOR91nt (SEQ ID NO: 95)ATGGTTCGTTACGTGCCCCGGTTCGCTGATGGTCAGAAAGTAAAGTTGGCTTGGCCCTTGGCGGTTTTTCGGTTAAATCACATATTCTGGCCATTGGATCCGAGCACAGGGAAATGGGGCCGATATCTGGACAAGGTTCTAGCTGTTGCGATGTCCTTGGTTTTTATGCAACACAACGATGCAGAGCTGAGGTACTTGCGCTTCGAGGCAAGTAATCGGAATTTGGATGCCTTTCTCACAGGAATGCCAACGTATTTAATCCTCGTGGAGGCTCAATTTAGAAGTCTTCACATTCTACTGCACTTCGAGAAGCTTCAGAAGTTTTTAGAAATATTCTACGCAAATATTTATATTGATCCCCGTAAGGAACCCGAAATGTTTCGAAAAGTGGATGGAAAGATGATAATTAACAGATTAGTTTCGGCCATGTACGGTGCAGTTATCTCTCTGTATCTAATCGCACCCGTTTTTTCCATCATTAACCAAAGCAAAGATTTTCTATACTCTATGATCTTTCCGTTCGATTCGGATCCCTTGTACATATTTGTGCCACTGCTTTTGACAAACGTATGGGTTGGCATTGTAATAGATACCATGATGTTCGGGGAGACGAATTTGTTGTGTGAACTAATTGTCCACCTAAATGGTAGTTATATGTTGCTCAAGAGGGACTTGCAGTTGGCCATTGAAAAGATATTAGTTGCAAGGGACCGTCCGCATATGGCCAAACAGCTAAAGGTTTTAATTACAAAAACTCTCCGAAAGAATGTGGCTCTAAATCAGTTTGGCCAGCAGCTGGAGGCTCAGTATACTGTGCGGGTTTTTATTATGTTTGCATTCGCTGCGGGCCTTTTATGTGCTCTTTCTTTTAAGGCTTATACGACGGATTCCCTCAGCACAATGTACTACCTTACCCATTGGGAGCAAATCCTGCAGTACTCTACAAATCCCAGCGAAAATCTGCGATTACTAAAGCTCATTAACTTGGCCATTGAGATGAACAGCAAGCCCTTCTATGTGACAGGGCTAAAATATTTTCGCGTTAGTCTGCAGGCTGGCTTAAAACGTCAAAAGTTTCTGCGGTCTGCCAGCTCATCCACCCTTAGCACCGCTGATGTGTTGGCATTTGCTTTTGCTTTTACTCGCTGGC TGCTT DOR92 (SEQ IDNO: 98) MSEWLRFLKRDQQLDVYFFAVPRLSLDIMGYWPGKTGDTWPWRSLIHFAILAIGVATELHAGMCFLDRQQITLALETLCPAGTSAVTLLKYFLMLRFRQDLSIMWNRLRGLLFDPNWERPEQRDIRLKHSAMAARINFWPLSAGFFTCTTYNLKPILIAMILYLQNRYEDFVWFTPFNMTMPKVLLNYPFFPLTYIFIAYTGYVTIFMFGGCDGFYFEFCAHLSALFEVLQAEIESMFRPYTDHLELSPVQLYILEQKMRSVIIRHNAIIDLTRFFRDRYTIITLAHFVSAAMVIGFSMVNLLTLGNNGLGAMLYVAYTVAALSQLLVYCYGGTLVAESSTGLCRAMFSCPWQLFKPKQRRLVQLLILRSQRPVSMAVPFFSPSLATFAAILQTSGSIIA LVKSFQ DOR92nt (SEQID NO: 97) ATGTCCGAGTGGTTACGCTTTCTGAAACGCGATCAACAGCTGGATGTGTACTTTTTTGCAGTGCCCCGCTTGAGTTTAGACATAATGGGCTATTGGCCGGGCAAAACTGGTGATACATGGCCCTGGAGATCCCTGATTCACTTCGCAATCCTGGCCATTGGCGTGGCCACCGAACTGCATGCTGGCATGTGTTTTCTAGACCGACAGCAGATTACCTTGGCACTGGAGACCCTCTGTCCAGCTGGCACATCGGCGGTCACGCTGCTCAAGATGTTCCTAATGCTGCGCTTTCGTCAGGATCTCTCCATTATGTGGAACCGCCTGAGGGGCCTGCTCTTCGATCCCAACTGGGAGCGACCCGAGCAGCGGGACATCCGGCTAAAGCACTCGGCCATGGCGGCTCGCATCAATTTCTGGCCCCTGTCAGCCGGATTCTTCACATGCACCACCTACAACCTAAAGCCGATACTGATCGCAATGATATTGTATCTCCAGAATCGTTACGAGGACTTCGTTTGGTTTACACCCTTCAATATGACTATGCCCAAAGTTCTGCTAAACTATCCATTTTTTCCCCTGACCTACATATTTATTGCCTATACGGGCTATGTGACCATCTTTATGTTCGGCGGCTGTGATGGTTTTTATTTCGAGTTCTGTGCCCACCTATCAGCTCTTTTCGAAGTGCTCCAGGCGGAGATAGAATCAATGTTTAGACCCTACACTGATCACTTGGAACTGTCGCCAGTGCAGCTTTACATTTTAGAGCAAAAGATGCGATCAGTAATCATTAGGCACAATGCCATCATCGATTTGACCAGATTTTTTCGTGATCGCTATACCATTATTACCCTGGCCCATTTTGTGTCCGCCGCCATGGTGATTGGATTCAGCATGGTTAATCTCCTGACATTGGGCAATAATGGTCTGGGCGCAATGCTCTATGTGGCCTACACGGTTGCCGCTTTGAGCCAACTGCTGGTTTATTGCTATGGCGGAACTCTGGTGGCCGAAAGTAGCACTGGTCTGTGCCGAGCCATGTTCTCCTGTCCGTGGCAGCTTTTTAAGCCTAAACAACGTCGACTCGTTCAGCTTTTGATTCTCAGATCGCAGCGTCCTGTTTCCATGGCAGTGCCATTCTTTTCGCCATCGTTGGCTACCTTTGCTGCGATTCTTCAAACTTCGGGTTCCATAATTGCG CTGGTTAAGTCCTTTCAGDOR95 (SEQ ID NO: 100)MSDKVKGKKQEEKDQSLRVQILVYRCMGIDLWSPTMANDRPWLTFVTMGPLFLFMVPMFLAAHEYITQVSLLSDTLGSTFASMLTLVKFLLFCYHRKEFVGLIYHIRAILAKEIEVWPDAREIIEVENQSDQMLSLTYTRCFGLAGIFAALKPFVGIILSSIRGDEIHLELPHNGVYPYDLQVVMFYVPTYLWNVMASYSAVTMALCVDSLLFFFTYNVCAIFKIAKHRMIHLPAVGGKEELEGLVQVLLLHQKGLQIADHIADKYRPLIFLQFFLSALQICFIGFQVADLFPNPQSLYFIAFVGSLLIALFIYSKCGENIKSASLDFGNGLYETNWTDFSPPTKRALLIAAMRAQRPCQMKGYFFEASMATFSTIVRSAVSYIMMLRSFNA DOR95nt (SEQ ID NO: 99)ATGAGCGACAAGGTGAAGGGAAAAAAGCAGGAGGAAAAGGATCAATCCTTGCGGGTGCAAATTCTCGTTTATCGCTGCATGGGCATCGATTTGTGGAGCCCCACGATGGCGAATGACCGCCCGTGGCTGACCTTTGTCACAATGGGACCACTTTTCCTGTTTATGGTGCCCATGTTCCTGGCCGCCCACGAGTACATCACCCAGGTGAGCCTGCTCTCCGACACCCTGGGCTCCACCTTCGCCAGCATGCTCACCCTGGTCAAATTCCTGCTCTTCTGCTATCATCGCAAGGAGTTCGTCGGCCTGATCTACCACATCAGGGCCATTCTGGCTAAAGAAATCGAAGTGTGGCCTGATGCGCGGGAAATCATCGAGGTGGAGAACCAAAGTGACCAAATGCTCAGTCTTACGTACACTCGCTGTTTTGGACTGGCTGGAATCTTTGCGGCCCTGAAGCCCTTTGTGGGCATCATACTCTCCTCGATTCGCGGCGACGAGATTCACCTGGAGCTGCCCCACAACGGCGTTTACCCGTACGATCTCCAGGTGGTCATGTTTTATGTGCCCACCTATCTGTGGAATGTGATGGCCAGCTATAGTGCTGTAACCATGGCACTCTGCGTGGACTCGCTGCTCTTCTTTTTCACCTACAACGTGTGCGCCATTTTCAAGATCGCCAAGCACCGGATGATCCATCTGCCGGCGGTGGGCGGAAAGGAGGAGCTGGAGGGGCTCGTCCAGGTGCTGCTGCTGCACCAGAAGGGCCTCCAGATCGCCGATCACATTGCGGACAAGTACCGGCCGCTGATCTTTTTGCAGTTCTTTCTGTCCGCCTTGCAGATCTGCTTCATTGGATTCCAGGTGGCTGATCTGTTTCCCAATCCGCAGAGTCTCTACTTTATCGCCTTTGTGGGCTCGCTGCTCATCGCACTGTTCATCTACTCGAAGTGCGGCGAAAATATCAAGAGTGCCAGCCTGGATTTCGGAAACGGGCTGTACGAGACCAACTGGACCGACTTCTCGCCACCCACTAAAAGAGCCCTCCTCATTGCCGCCATGCGCGCCCAGCGACCTTGCCAGATGAAGGGCTACTTTTTCGAGGCCAGCATGGCCACCTTCTCGACGATTGTTCGCTCTGCCGTGTCGTACATCATGATGTTGCGCTCCTTTAATGCC DOR99 (SEQ ID NO: 102)MEEFLRPQMFQEVAQMVHFQWRRNPVDNSMVNASMVPFCLSAFLNVLFFGCNGWDIIGHFWLGHPANQNPPVLSITIYFSIRGLMLYLKRKEIVEFVNDLDRECPRDLVSQLDMQMDETYRNFWQRYRFIRIYSHLGGPMFCVVPLALFLLTHEGKDTPVAQHEQLLGGWLPCGVRKDPNFYLLVWSFDLMCTTCGVSFFVTFDNLFNVMQGHLVMHLGHLARQFSAIDPRQSLTDEKRFFVDLRLLVQRQQLLNGLCRKYNDIFKVAFLVSNFVGAGSLCFYLFMLSETSDVLIIAQYILPTLVLVGFTFEICLRGTQLEKASEGLESSLRSQEWYLGSRRYRKFYLLWTQYCQRTQQLGAFGLIQVNMVHFTEIMQLAYRLFTFLKSH DOR99nt (SEQ ID NO: 101)ATGGAGGAGTTTCTGCGTCCGCAGATGTTCCAGGAGGTGGCTCAGATGGTGCATTTCCAGTGGCGGAGAAATCCGGTGGACAACAGCATGGTGAACGCATCCATGGTCCCCTTCTGCTTGTCGGCGTTTCTTAATGTCCTGTTTTTCGGCTGCAATGGTTGGGACATCATAGGACATTTTTGGCTGGGACATCCTGCCAACCAGAATCCGCCCGTGCTTAGCATCACCATTTACTTCTCGATCAGGGGATTGATGCTATACCTGAAACGAAAGGAAATCGTTGAGTTTGTTAACGACTTGGATCGGGAGTGTCCGCGGGACTTGGTCAGCCAGTTGGACATGCAAATGGATGAGACGTACCGAAACTTTTGGCAGCGCTATCGCTTCATCCGTATCTACTCCCATTTGGGTGGTCCGATGTTCTGCGTTGTGCCATTAGCTCTATTCCTCCTGACCCACGAGGGTAAAGATACTCCTGTTGCCCAGCACGAGCAGCTCCTTGGAGGATGGCTGCCATGCGGTGTGCGAAAGGACCCAAATTTCTACCTTTTAGTCTGGTCCTTCGACCTGATGTGCACCACTTGCGGCGTCTCCTTTTTCGTTACCTTCGACAACCTATTCAATGTGATGCAGGGACATTTGGTCATGCATTTGGGCCATCTTGCTCGCCAGTTTTCGGCCATCGATCCTCGACAGAGTTTGACCGATGAGAAGCGATTCTTTGTGGATCTTAGGTTATTAGTTCAGAGGCAGCAGCTTCTTAATGGATTGTGCAGAAAATACAACGACATCTTTAAAGTGGCCTTCCTGGTGAGCAATTTTGTAGGCGCCGGTTCCCTCTGCTTCTACCTCTTTATGCTCTCGGAGACATCAGATGTCCTTATCATCGCCCAGTATATATTACCCACTTTGGTCCTGGTGGGCTTCACATTTGAGATTTGTCTACGGGGAACCCAACTGGAAAAGGCGTCGGAGGGACTGGAATCGTCGTTGCGAAGCCAGGAATGGTATTTGGGAAGTAGGCGGTACCGGAAGTTCTATTTGCTCTGGACGCAATATTGCCAGCGAACACAGCAACTGGGCGCCTTTGGGCTAATCCAAGTCAATATGGTGCACTTCACTGAAATAATGCAGCTGGCCTATAGACTCT TCACTTTTCTCAAATCTCATDORA45 (SEQ ID NO: 104)MTTSMQPSKYTGLVADLMPNIRAMKYSGLFMHNFTGGSAFMKKVYSSVHLVFLLMQFTFILVNMALNAEEVNELSGNTITTLFFTHCITKFIYLAVNQKNFYRTLNIWNQVNTHPLFAESDARYHSIALAKMRKLFFLVMLTTVASATAWTTITFFGDSVKMVVDHETNSSIPVEIPRLPIKSFYPWNASHGMFYMISFAFQIYYVLFSMIHSNLCDVMFCSWLIFACEQLQHLKGIMKPLMELSASLDTYRPNSAALFRSLSANSKSELIHNEEKDPGTDMDMSGIYSSKADWGAQFRAPSTLQSFGGNGGGGNGLVNGANPNGLTKKQEMMVRSAIKYWVERHKHVVRLVAAIGDTYGAALLLHMLTSTIKLTLLAYQATKINGVNVYAFTVVGYLGYALAQVFHFCIFGNRLIEESSSVMEAAYSCHWYDGSEEAKTFVQIVCQQCQKAMSISGAKFFTVSLDLFASVLGAVVTYFMVLVQLK DORA45nt (SEQ ID NO: 103)GGCACGAGCTGGTTCCGGAAAGCCTCATATCTCGTATCTTAAAGTATCCCGGTTAAGCCTTAAAGAGTGAAATGATTGCCTAGACGATTGCTGCATTACTGGCACTCAATTAACCCAAGTGTACCAGACAACAATTACATTTGTATTTTTAAAGTTCAATAGCAAGGATGACAACCTCGATGCAGCCGAGCAAGTACACGGGCCTGGTCGCCGACCTGATGCCCAACATCCGGGCGATGAAGTACTCCGGCCTGTTCATGCACAACTTCACGGGCGGCAGTGCCTTCATGAAGAAGGTGTACTCCTCCGTGCACCTGGTGTTCCTCCTCATGCAGTTCACCTTCATCCTGGTCAACATGGCCCTGAACGCCGAGGAGGTCAACGAGCTGTCGGGCAACACGATCACGACCCTCTTCTTCACCCACTGCATCACGAAGTTTATCTACCTGGCTGTTAACCAGAAGAATTTCTACAGAACATTGAATATATGGAACCAGGTGAACACGCATCCCTTGTTCGCCGAGTCGGATGCTCGTTACCATTCGATCGCACTGGCGAAGATGAGGAAGCTGTTCTTTCTGGTGATGCTGACCACAGTCGCCTCGGCCACCGCCTGGACCACGATCACCTTCTTTGGCGACAGCGTAAAAATGGTGGTGGACCATGAGACGAACTCCAGCATCCCGGTGGAGATACCCCGGCTGCCGATTAAGTCCTTCTACCCGTGGAACGCCAGCCACGGCATGTTCTACATGATCAGCTTTGCCTTTCAGATCTACTACGTGCTCTTCTCGATGATCCACTCCAATCTATGCGACGTGATGTTCTGCTCTTGGCTGATATTCGCCTGCGAGCAGCTGCAGCACTTGAAGGGCATCATGAAGCCGCTGATGGAGCTGTCCGCCTCGCTGGACACCTACAGGCCCAACTCGGCGGCCCTCTTCAGGTCCCTGTCGGCCAACTCCAAGTCGGAGCTAATTCATAATGAAGAAAAGGATCCCGGCACCGACATGGACATGTCCGGCATCTACAGCTCGAAAGCGGATTGGGGCGCTCAGTTTCGAGCACCCTCGACACTGCAGTCCTTTGGCGGGAACGGGGGCGGAGGCAACGGGTTGGTGAACGGCGCTAATCCCAACGGGCTGACCAAAAAGCAGGAGATGATGGTGCGCAGTGCCATCAAGTACTGGGTCGAGCGGCACAAGCACGTGGTGCGACTGGTGGCTGCCATCGGCGATACTTACGGAGCCGCCCTCCTCCTCCACATGCTGACCTCGACCATCAAGCTCACCCTGCTGGCATACCAGGCCACCAAAATCAACGGAGTGAATGTCTACGCCTTCACAGTCGTCGGATACCTAGGATACGCGCTGGCCCAGGTGTTCCACTTTTGCATCTTTGGCAATCGTCTGATTGAAGAGAGTTCATCCGTCATGGAGGCCGCCTACTCGTGCCACTGGTACGATGGCTCCGAGGAGGCCAAGACCTTCGTCCAGATCGTGTGCCAGCAGTGCCAGAAGGCGATGAGCATATCGGGAGCGAAATTCTTCACCGTCTCCCTGGATTTGTTTGCTTCGGTTCTGGGTGCCGTCGTCACCTACTTTATGGTGCTGGTGCAGCTCAAGTAAGTTGCTGCGAAGCTGATGGATTTTTGTACCAGAAAAGCGAATGCCAAGAAGCCACCTACCGCCCCTTGCCCCCTCCGCACTGTGCAACCAGCAATATCACAGAGCAATTATAACGCAAATTATATATTTTATACCTGCGACGAGCGAGCCTCGTGGGGCATAATGGAGACATTCTGGGGCACATAGAAGCCTGCAAATACTTATCGATTTTGTACACGCGTAGAGCTTTTAATGTAAACTCAAGATGCAAACTAAATAAATGTGTAGTGAAA AAAAAAAAAAAAAAAAAGenbank Accession Numbers

The accession numbers for the sequences reported in this paper areAF127921-AF127926.

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1-4. (canceled)
 5. An isolated nucleic acid encoding a polypeptide present in an insect odorant receptor, wherein the polypeptide is selected from the group consisting of polypeptides comprising consecutive amino acids the sequence of which is one of the following: (a) SEQ ID NO: 2, (b) SEQ ID NO: 4, (c) SEQ ID NO: 6, (d) SEQ ID NO: 8, (e) SEQ ID NO: 10, (f) SEQ ID NO: 12, (g) SEQ ID NO: 14, (h) SEQ ID NO: 16, (i) SEQ ID NO: 18, (j) SEQ ID NO: 20, (k) SEQ ID NO: 22, (l) SEQ ID NO: 24, (m) SEQ ID NO: 26, (n) SEQ ID NO: 28, (o) SEQ ID NO: 30, (p) SEQ ID NO: 32, (q) SEQ ID NO: 34, (r) SEQ ID NO: 36, (s) SEQ ID NO: 38, (t) SEQ ID NO: 40, (u) SEQ ID NO: 42, (v) SEQ ID NO: 44, (w) SEQ ID NO: 46, (x) SEQ ID NO: 48, (y) SEQ ID NO: 50, (z) SEQ ID NO: 52, (aa) SEQ ID NO: 54, (bb) SEQ ID NO: 56, (cc) SEQ ID NO: 58, (dd) SEQ ID NO: 60, (ee) SEQ ID NO: 62, (ff) SEQ ID NO: 64, (gg) SEQ ID NO: 66, (hh) SEQ ID NO: 68, (ii) SEQ ID NO: 70, (jj) SEQ ID NO: 72, (kk) SEQ ID NO: 74, (ll) SEQ ID NO: 76, (mm) SEQ ID NO: 78, (nn) SEQ ID NO: 80, (oo) SEQ ID NO: 82, (pp) SEQ ID NO: 84, (qq) SEQ ID NO: 86, (rr) SEQ ID NO: 88, (ss) SEQ ID NO: 90, (tt) SEQ ID NO: 92, (uu) SEQ ID NO: 94, (vv) SEQ ID NO: 96, (ww) SEQ ID NO: 98, (xx) SEQ ID NO: 100, (yy) SEQ ID NO: 102, (zz) SEQ ID NO: 106, or (aaa) a polypeptide which shares greater than 25% amino acid identity with any one of the polypeptides of (a)-(aaa), and comprises a transmembrane domain and an adjoining C-terminal domain which together comprise consecutive amino acids the sequence of which is as follows: —(F, Y, L, A, T, S or C)—(P, I, M, V, T, L, Q, S or H)—(F, Y, I, S, L, C, M or V)—(C, Y, T, S, L or A)-(Y, N, F, M, I, L, K, S, H or T)-(X)₂₀—W— (SEQ ID NO: 107); wherein each X in (X) 20 represents an amino acid and the identity of each X is independent of the identity of any other X. 6-10. (canceled)
 11. An isolated nucleic acid encoding a polypeptide present in an insect odorant receptor, wherein the nucleic acid hybridizes under high stringency to a complement of a nucleic acid of claim
 5. 12. (canceled)
 13. An isolated nucleic acid encoding a polypeptide present in an insect odorant receptor, wherein the nucleic acid comprises: (a) a nucleic acid sequence given in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, or 105; or (b) a nucleic acid sequence degenerate to a sequence of (a) as a result of the genetic code.
 14. The isolated nucleic acid of claim 13, wherein the insect odorant receptor comprises seven transmembrane domains.
 15. The isolated nucleic acid of claim 5, wherein the nucleic acid is DNA or RNA.
 16. The isolated nucleic acid of claim 15, wherein the DNA is cDNA, genomic DNA, or synthetic DNA.
 17. The isolated nucleic acid of claim 5, wherein the nucleic acid encodes a Drosophila odorant receptor. 18-19. (canceled)
 20. A vector which comprises the isolated nucleic acid of claim
 5. 21-34. (canceled)
 35. A method of transforming a cell which comprises transfecting a host cell with the vector of claim
 20. 36. A transformed cell produced by the method of claim
 35. 37. The transformed cell of claim 36, wherein prior to being transfected with the vector the host cell does not express an insect odorant receptor.
 38. The transformed cell of claim 36, wherein prior to being transfected with the vector the host cell does express an insect odorant receptor. 39-54. (canceled)
 55. The isolated nucleic acid of claim 11, wherein the nucleic acid is DNA or RNA.
 56. The isolated nucleic acid of claim 11, wherein the DNA is cDNA, genomic DNA, or synthetic DNA.
 57. The isolated nucleic acid of claim 11, wherein the nucleic acid encodes a Drosophila odorant receptor.
 58. A vector which comprises the isolated nucleic acid of claim
 11. 59. The isolated nucleic acid of claim 13, wherein the nucleic acid is DNA or RNA.
 60. The isolated nucleic acid of claim 13, wherein the DNA is cDNA, genomic DNA, or synthetic DNA.
 61. The isolated nucleic acid of claim 13, wherein the nucleic acid encodes a Drosophila odorant receptor.
 62. A vector which comprises the isolated nucleic acid of claim
 13. 